rs680638

Variant names:

• chr1-186187382-C-T
• rs680638
• NM_031935.3:c.16415-501C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031935.3(HMCN1):​c.16415-501C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 152,002 control chromosomes in the GnomAD database, including 50,818 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 0.81 (50818 hom., cov: 30)
• Consequence: HMCN1 NM_031935.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.245
• Publications: 6 publications found

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)

ENSG00000294274 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMCN1	NM_031935.3	c.16415-501C>T		intron_variant	Intron 105 of 106	ENST00000271588.9	NP_114141.2
HMCN1	XM_011510038.4	c.16064-501C>T		intron_variant	Intron 104 of 105		XP_011508340.1
HMCN1	XM_017002437.2	c.14438-501C>T		intron_variant	Intron 94 of 95		XP_016857926.1
HMCN1	XM_047431608.1	c.12239-501C>T		intron_variant	Intron 82 of 83		XP_047287564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMCN1	ENST00000271588.9	c.16415-501C>T		intron_variant	Intron 105 of 106	1	NM_031935.3	ENSP00000271588.4
HMCN1	ENST00000414277.1	c.440-501C>T		intron_variant	Intron 4 of 5	3		ENSP00000406205.1
ENSG00000294274	ENST00000722342.1	n.238+34374G>A		intron_variant	Intron 1 of 3
ENSG00000294274	ENST00000722343.1	n.253-2127G>A		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.812 AC: 123328 AN: 151884 Hom.: 50752 Cov.: 30

Gnomad AFR AF: 0.950

Gnomad AMI AF: 0.850

Gnomad AMR AF: 0.792

Gnomad ASJ AF: 0.801

Gnomad EAS AF: 0.655

Gnomad SAS AF: 0.727

Gnomad FIN AF: 0.733

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.789

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

GnomAD4 genome AF: 0.812 AC: 123453 AN: 152002 Hom.: 50818 Cov.: 30 AF XY: 0.807 AC XY: 59928 AN XY: 74296

African (AFR) AF: 0.950 AC: 39432 AN: 41506

American (AMR) AF: 0.792 AC: 12087 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.801 AC: 2780 AN: 3470

East Asian (EAS) AF: 0.656 AC: 3374 AN: 5144

South Asian (SAS) AF: 0.726 AC: 3485 AN: 4800

European-Finnish (FIN) AF: 0.733 AC: 7748 AN: 10564

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.763 AC: 51856 AN: 67942

Other (OTH) AF: 0.791 AC: 1667 AN: 2108

Alfa AF: 0.779 Hom.: 73649

Bravo AF: 0.826

Asia WGS AF: 0.731 AC: 2543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.58
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs680638; hg19: chr1-186156514;