dbSNP rs2891230: HMCN1:c.12094+58G>A (chr1-186119940-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_031935.3(HMCN1):c.12094+58G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 1,613,322 control chromosomes in the GnomAD database, including 98,937 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.34 ( 9092 hom., cov: 32)

Exomes 𝑓: 0.34 ( 89845 hom. )

Consequence

HMCN1
NM_031935.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.11

Publications

13 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: AD, Unknown Classification: LIMITED Submitted by: Laboratory for Molecular Medicine, Ambry Genetics, Labcorp Genetics (formerly Invitae)

HMCN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.53 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.12094+58G>A		intron	N/A	NP_114141.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMCN1	ENST00000271588.9	TSL:1 MANE Select	c.12094+58G>A		intron	N/A	ENSP00000271588.4

Frequencies

GnomAD3 genomes

AF:

0.336

AC:

50999

AN:

151704

Hom.:

9060

Cov.:

show subpopulations

Gnomad AFR

AF:

0.251

Gnomad AMI

AF:

0.219

Gnomad AMR

AF:

0.461

Gnomad ASJ

AF:

0.327

Gnomad EAS

AF:

0.547

Gnomad SAS

AF:

0.415

Gnomad FIN

AF:

0.386

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.333

Gnomad OTH

AF:

0.337

GnomAD4 exome

AF:

0.345

AC:

504216

AN:

1461508

Hom.:

89845

Cov.:

AF XY:

0.346

AC XY:

251919

AN XY:

727062

show subpopulations

African (AFR)

AF:

0.260

AC:

8684

AN:

33458

American (AMR)

AF:

0.557

AC:

24896

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.333

AC:

8695

AN:

26128

East Asian (EAS)

AF:

0.521

AC:

20697

AN:

39694

South Asian (SAS)

AF:

0.402

AC:

34636

AN:

86222

European-Finnish (FIN)

AF:

0.378

AC:

20208

AN:

53414

Middle Eastern (MID)

AF:

0.383

AC:

2206

AN:

5766

European-Non Finnish (NFE)

AF:

0.327

AC:

363099

AN:

1111746

Other (OTH)

AF:

0.349

AC:

21095

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

19756

39512

59267

79023

98779

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12024

24048

36072

48096

60120

<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:

0.336

AC:

51060

AN:

151814

Hom.:

9092

Cov.:

AF XY:

0.342

AC XY:

25369

AN XY:

74166

show subpopulations

African (AFR)

AF:

0.251

AC:

10409

AN:

41392

American (AMR)

AF:

0.462

AC:

7055

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.327

AC:

1133

AN:

3468

East Asian (EAS)

AF:

0.547

AC:

2822

AN:

5162

South Asian (SAS)

AF:

0.415

AC:

1994

AN:

4802

European-Finnish (FIN)

AF:

0.386

AC:

4038

AN:

10466

Middle Eastern (MID)

AF:

0.286

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.333

AC:

22598

AN:

67944

Other (OTH)

AF:

0.345

AC:

728

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1714

3428

5141

6855

8569

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

502

1004

1506

2008

2510

<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:

0.353

Hom.:

1564

Bravo

AF:

0.342

Asia WGS

AF:

0.465

AC:

1616

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

5.4

(source)

DANN

Benign

0.62

PhyloP100

2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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