rs12080760

Positions:

• chr1-186140164-G-T

Variant summary

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

The NM_031935.3(HMCN1):​c.13924+2192G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 151,856 control chromosomes in the GnomAD database, including 17,784 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 0.46 (17784 hom., cov: 31)
• Consequence: HMCN1 NM_031935.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.18

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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMCN1	NM_031935.3	c.13924+2192G>T		intron_variant		ENST00000271588.9
HMCN1	XM_011510038.4	c.13924+2192G>T		intron_variant
HMCN1	XM_017002437.2	c.11947+2192G>T		intron_variant
HMCN1	XM_047431608.1	c.9748+2192G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMCN1	ENST00000271588.9	c.13924+2192G>T		intron_variant		1	NM_031935.3	P1

Frequencies

GnomAD3 genomes AF: 0.461 AC: 69978 AN: 151738 Hom.: 17719 Cov.: 31

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.412

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

GnomAD4 genome AF: 0.462 AC: 70101 AN: 151856 Hom.: 17784 Cov.: 31 AF XY: 0.465 AC XY: 34494 AN XY: 74194

Gnomad4 AFR AF: 0.665

Gnomad4 AMR AF: 0.509

Gnomad4 ASJ AF: 0.345

Gnomad4 EAS AF: 0.576

Gnomad4 SAS AF: 0.451

Gnomad4 FIN AF: 0.402

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.418

Alfa AF: 0.380 Hom.: 6018

Bravo AF: 0.481

Asia WGS AF: 0.513 AC: 1786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.22
DANN	Benign	0.29

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

LitVar

Other links and lift over

dbSNP: rs12080760; hg19: chr1-186109296;