rs4650695

Positions:

• chr1-186140693-T-A
• chr1-186140693-T-G

Variant summary

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

The NM_031935.3(HMCN1):​c.13924+2721T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 151,932 control chromosomes in the GnomAD database, including 13,370 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 0.41 (13370 hom., cov: 32)
• Consequence: HMCN1 NM_031935.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMCN1	NM_031935.3	c.13924+2721T>A		intron_variant		ENST00000271588.9
HMCN1	XM_011510038.4	c.13924+2721T>A		intron_variant
HMCN1	XM_017002437.2	c.11947+2721T>A		intron_variant
HMCN1	XM_047431608.1	c.9748+2721T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMCN1	ENST00000271588.9	c.13924+2721T>A		intron_variant		1	NM_031935.3	P1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62253 AN: 151814 Hom.: 13328 Cov.: 32

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.410 AC: 62333 AN: 151932 Hom.: 13370 Cov.: 32 AF XY: 0.414 AC XY: 30749 AN XY: 74250

Gnomad4 AFR AF: 0.485

Gnomad4 AMR AF: 0.494

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.578

Gnomad4 SAS AF: 0.449

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.389

Alfa AF: 0.255 Hom.: 614

Bravo AF: 0.424

Asia WGS AF: 0.500 AC: 1738 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.8
DANN	Benign	0.84

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: rs4650695; hg19: chr1-186109825;