dbSNP rs10489753: HMCN1:c.13924+1568G>A (chr1-186139540-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_031935.3(HMCN1):c.13924+1568G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0352 in 150,104 control chromosomes in the GnomAD database, including 137 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 0.035 ( 137 hom., cov: 32)

Consequence

HMCN1
NM_031935.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.286

Publications

0 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:

ENSG00000294274 (HGNC:):

ENSG00000294274 links:

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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=-0.82).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0352 (5279/150104) while in subpopulation NFE AF = 0.0499 (3376/67668). AF 95% confidence interval is 0.0485. There are 137 homozygotes in GnomAd4. There are 2510 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 5279 AD,Unknown gene.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMCN1	NM_031935.3	MANE Select	c.13924+1568G>A		intron	N/A	NP_114141.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMCN1	ENST00000271588.9	TSL:1 MANE Select	c.13924+1568G>A		intron	N/A	ENSP00000271588.4
	ENSG00000294274	ENST00000722342.1		n.239-1607C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0352

AC:

5277

AN:

150078

Hom.:

136

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00818

Gnomad AMI

AF:

0.0220

Gnomad AMR

AF:

0.0377

Gnomad ASJ

AF:

0.0604

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.0281

Gnomad FIN

AF:

0.0510

Gnomad MID

AF:

0.0942

Gnomad NFE

AF:

0.0499

Gnomad OTH

AF:

0.0509

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0352

AC:

5279

AN:

150104

Hom.:

137

Cov.:

AF XY:

0.0343

AC XY:

2510

AN XY:

73110

show subpopulations

African (AFR)

AF:

0.00817

AC:

334

AN:

40898

American (AMR)

AF:

0.0377

AC:

568

AN:

15078

Ashkenazi Jewish (ASJ)

AF:

0.0604

AC:

209

AN:

3458

East Asian (EAS)

AF:

0.000195

AC:

AN:

5136

South Asian (SAS)

AF:

0.0284

AC:

135

AN:

4746

European-Finnish (FIN)

AF:

0.0510

AC:

503

AN:

9854

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.0499

AC:

3376

AN:

67668

Other (OTH)

AF:

0.0507

AC:

105

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

260

519

779

1038

1298

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<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:

0.0442

Hom.:

Bravo

AF:

0.0327

Asia WGS

AF:

0.0120

AC:

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.4

(source)

DANN

Benign

0.18

PhyloP100

0.29

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over