rs13375391

Positions:

• chr1-185825751-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_031935.3(HMCN1):​c.269-20275G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 152,272 control chromosomes in the GnomAD database, including 41 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 0.012 (41 hom., cov: 32)
• Consequence: HMCN1 NM_031935.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0121 (1835/152272) while in subpopulation AFR AF= 0.0415 (1726/41560). AF 95% confidence interval is 0.0399. There are 41 homozygotes in gnomad4. There are 860 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1835 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMCN1	NM_031935.3	c.269-20275G>A		intron_variant		ENST00000271588.9	NP_114141.2
HMCN1	XM_011510038.4	c.269-20275G>A		intron_variant			XP_011508340.1
HMCN1	XM_011510041.4	c.269-20275G>A		intron_variant			XP_011508343.1
HMCN1	XM_024450118.2	c.269-20275G>A		intron_variant			XP_024305886.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMCN1	ENST00000271588.9	c.269-20275G>A		intron_variant		1	NM_031935.3	ENSP00000271588	P1

Frequencies

GnomAD3 genomes AF: 0.0120 AC: 1829 AN: 152154 Hom.: 41 Cov.: 32

Gnomad AFR AF: 0.0415

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00485

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.0105

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

GnomAD4 genome AF: 0.0121 AC: 1835 AN: 152272 Hom.: 41 Cov.: 32 AF XY: 0.0115 AC XY: 860 AN XY: 74464

Gnomad4 AFR AF: 0.0415

Gnomad4 AMR AF: 0.00484

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00282 Hom.: 6

Bravo AF: 0.0143

Asia WGS AF: 0.00202 AC: 7 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	17
DANN	Benign	0.68

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: rs13375391; hg19: chr1-185794883;