1-186126369-A-T

Variant summary

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

The NM_031935.3(HMCN1):c.12690+575A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 151,870 control chromosomes in the GnomAD database, including 17,887 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 0.47 (17887 hom., cov: 32)
• Consequence: HMCN1 NM_031935.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMCN1	NM_031935.3	c.12690+575A>T		intron_variant		ENST00000271588.9
HMCN1	XM_011510038.4	c.12690+575A>T		intron_variant
HMCN1	XM_017002437.2	c.10713+575A>T		intron_variant
HMCN1	XM_047431608.1	c.8514+575A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMCN1	ENST00000271588.9	c.12690+575A>T		intron_variant		1	NM_031935.3	P1

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70742 AN: 151750 Hom.: 17824 Cov.: 32

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.605

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.432

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

GnomAD4 genome AF: 0.467 AC: 70865 AN: 151870 Hom.: 17887 Cov.: 32 AF XY: 0.469 AC XY: 34836 AN XY: 74226

Gnomad4 AFR AF: 0.643

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.359

Gnomad4 EAS AF: 0.604

Gnomad4 SAS AF: 0.484

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.440

Alfa AF: 0.283 Hom.: 706

Bravo AF: 0.486

Asia WGS AF: 0.568 AC: 1975 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	7.7
Dann	Benign	0.77

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: rs6659783; hg19: chr1-186095501;