rs10911825

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_031935.3(HMCN1):c.13310A>G(p.Gln4437Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.303 in 1,604,574 control chromosomes in the GnomAD database, including 83,905 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q4437L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.39 ( 13644 hom., cov: 32)

Exomes 𝑓: 0.29 ( 70261 hom. )

Consequence

HMCN1
NM_031935.3 missense

Scores

Splicing: ADA: 0.1729

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 8.50

Publications

34 publications found

Variant links:

Genes affected

HMCN1 (HGNC:19194): (hemicentin 1) This gene encodes a large extracellular member of the immunoglobulin superfamily. A similar protein in C. elegans forms long, fine tracks at specific extracellular sites that are involved in many processes such as stabilization of the germline syncytium, anchorage of mechanosensory neurons to the epidermis, and organization of hemidesmosomes in the epidermis. Mutations in this gene may be associated with age-related macular degeneration. [provided by RefSeq, Jul 2008]

HMCN1 Gene-Disease associations (from GenCC):

age related macular degeneration 1
Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine

HMCN1 links:

ENSG00000294274 (HGNC:):

ENSG00000294274 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.746112E-5).

BP6

Variant 1-186132407-A-G is Benign according to our data. Variant chr1-186132407-A-G is described in ClinVar as Benign. ClinVar VariationId is 294262.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031935.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMCN1	NM_031935.3	MANE Select	c.13310A>G	p.Gln4437Arg	missense	Exon 86 of 107	NP_114141.2	Q96RW7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMCN1	ENST00000271588.9	TSL:1 MANE Select	c.13310A>G	p.Gln4437Arg	missense	Exon 86 of 107	ENSP00000271588.4	Q96RW7-1
	ENSG00000294274	ENST00000722342.1		n.588+3887T>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.394

AC:

59768

AN:

151826

Hom.:

13586

Cov.:

show subpopulations

Gnomad AFR

AF:

0.587

Gnomad AMI

AF:

0.111

Gnomad AMR

AF:

0.458

Gnomad ASJ

AF:

0.311

Gnomad EAS

AF:

0.603

Gnomad SAS

AF:

0.405

Gnomad FIN

AF:

0.355

Gnomad MID

AF:

0.283

Gnomad NFE

AF:

0.261

Gnomad OTH

AF:

0.365

GnomAD2 exomes

AF:

0.380

AC:

93007

AN:

244910

AF XY:

0.364

show subpopulations

Gnomad AFR exome

AF:

0.600

Gnomad AMR exome

AF:

0.571

Gnomad ASJ exome

AF:

0.323

Gnomad EAS exome

AF:

0.605

Gnomad FIN exome

AF:

0.350

Gnomad NFE exome

AF:

0.263

Gnomad OTH exome

AF:

0.336

GnomAD4 exome

AF:

0.294

AC:

427079

AN:

1452626

Hom.:

70261

Cov.:

AF XY:

0.295

AC XY:

213312

AN XY:

722632

show subpopulations

African (AFR)

AF:

0.609

AC:

20275

AN:

33270

American (AMR)

AF:

0.561

AC:

24759

AN:

44158

Ashkenazi Jewish (ASJ)

AF:

0.315

AC:

8178

AN:

26000

East Asian (EAS)

AF:

0.568

AC:

22370

AN:

39408

South Asian (SAS)

AF:

0.390

AC:

33356

AN:

85532

European-Finnish (FIN)

AF:

0.344

AC:

18292

AN:

53112

Middle Eastern (MID)

AF:

0.331

AC:

1902

AN:

5752

European-Non Finnish (NFE)

AF:

0.252

AC:

278581

AN:

1105448

Other (OTH)

AF:

0.323

AC:

19366

AN:

59946

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

13197

26394

39591

52788

65985

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9830

19660

29490

39320

49150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.394

AC:

59886

AN:

151948

Hom.:

13644

Cov.:

AF XY:

0.399

AC XY:

29603

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.587

AC:

24341

AN:

41456

American (AMR)

AF:

0.459

AC:

6991

AN:

15232

Ashkenazi Jewish (ASJ)

AF:

0.311

AC:

1079

AN:

3472

East Asian (EAS)

AF:

0.603

AC:

3108

AN:

5158

South Asian (SAS)

AF:

0.404

AC:

1942

AN:

4810

European-Finnish (FIN)

AF:

0.355

AC:

3747

AN:

10548

Middle Eastern (MID)

AF:

0.288

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.261

AC:

17706

AN:

67956

Other (OTH)

AF:

0.373

AC:

787

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1651

3302

4954

6605

8256

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

540

1080

1620

2160

2700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.317

Hom.:

28433

Bravo

AF:

0.416

TwinsUK

AF:

0.247

AC:

917

ALSPAC

AF:

0.244

AC:

941

ESP6500AA

AF:

0.579

AC:

2553

ESP6500EA

AF:

0.263

AC:

2258

ExAC

AF:

0.370

AC:

44817

Asia WGS

AF:

0.536

AC:

1862

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Age related macular degeneration 1 (3)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.58

MetaRNN

Benign

0.000077

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.65

PhyloP100

8.5

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.14

Sift

Benign

0.35

Sift4G

Uncertain

0.0020

Polyphen

0.73

Vest4

0.24

MPC

0.26

ClinPred

0.021

GERP RS

5.4

Varity_R

0.59

gMVP

0.58

Mutation Taster

=87/13

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.17

dbscSNV1_RF

Benign

0.43

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over