1-186083830-C-G

Position:

• chr1-186083830-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031935.3(HMCN1):​c.8884+869C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 151,964 control chromosomes in the GnomAD database, including 33,668 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 0.64 (33668 hom., cov: 32)
• Consequence: HMCN1 NM_031935.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.953

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMCN1	NM_031935.3	c.8884+869C>G		intron_variant		ENST00000271588.9	NP_114141.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMCN1	ENST00000271588.9	c.8884+869C>G		intron_variant		1	NM_031935.3	ENSP00000271588.4

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97678 AN: 151844 Hom.: 33591 Cov.: 32

Gnomad AFR AF: 0.906

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.611

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

GnomAD4 genome AF: 0.644 AC: 97818 AN: 151964 Hom.: 33668 Cov.: 32 AF XY: 0.643 AC XY: 47747 AN XY: 74238

Gnomad4 AFR AF: 0.906

Gnomad4 AMR AF: 0.651

Gnomad4 ASJ AF: 0.586

Gnomad4 EAS AF: 0.629

Gnomad4 SAS AF: 0.610

Gnomad4 FIN AF: 0.536

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.615

Alfa AF: 0.415 Hom.: 1036

Bravo AF: 0.665

Asia WGS AF: 0.654 AC: 2269 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.070
DANN	Benign	0.088

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: rs10798036; hg19: chr1-186052962;