rs680638

Positions:

• chr1-186187382-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
HMCN1	NM_031935.3	c.16415-501C>T		intron_variant		ENST00000271588.9	NP_114141.2
HMCN1	XM_011510038.4	c.16064-501C>T		intron_variant			XP_011508340.1
HMCN1	XM_017002437.2	c.14438-501C>T		intron_variant			XP_016857926.1
HMCN1	XM_047431608.1	c.12239-501C>T		intron_variant			XP_047287564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMCN1	ENST00000271588.9	c.16415-501C>T		intron_variant		1	NM_031935.3	ENSP00000271588.4
HMCN1	ENST00000414277.1	c.440-501C>T		intron_variant		3		ENSP00000406205.1

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

Gnomad4 AFR AF: 0.950

Gnomad4 AMR AF: 0.792

Gnomad4 ASJ AF: 0.801

Gnomad4 EAS AF: 0.656

Gnomad4 SAS AF: 0.726

Gnomad4 FIN AF: 0.733

Gnomad4 NFE AF: 0.763

Gnomad4 OTH AF: 0.791

Alfa AF: 0.774 Hom.: 52705

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

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

LitVar

Other links and lift over

dbSNP: rs680638; hg19: chr1-186156514;