rs10489753

Positions:

• chr1-186139540-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_031935.3(HMCN1):​c.13924+1568G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0352 in 150,104 control chromosomes in the GnomAD database, including 137 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 0.035 (137 hom., cov: 32)
• Consequence: HMCN1 NM_031935.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.286

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=-0.82).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0352 (5279/150104) while in subpopulation NFE AF= 0.0499 (3376/67668). AF 95% confidence interval is 0.0485. There are 137 homozygotes in gnomad4. There are 2510 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 5279 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMCN1	NM_031935.3	c.13924+1568G>A		intron_variant		ENST00000271588.9	NP_114141.2
HMCN1	XM_011510038.4	c.13924+1568G>A		intron_variant			XP_011508340.1
HMCN1	XM_017002437.2	c.11947+1568G>A		intron_variant			XP_016857926.1
HMCN1	XM_047431608.1	c.9748+1568G>A		intron_variant			XP_047287564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMCN1	ENST00000271588.9	c.13924+1568G>A		intron_variant		1	NM_031935.3	ENSP00000271588.4

Frequencies

GnomAD3 genomes AF: 0.0352 AC: 5277 AN: 150078 Hom.: 136 Cov.: 32

Gnomad AFR AF: 0.00818

Gnomad AMI AF: 0.0220

Gnomad AMR AF: 0.0377

Gnomad ASJ AF: 0.0604

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.0281

Gnomad FIN AF: 0.0510

Gnomad MID AF: 0.0942

Gnomad NFE AF: 0.0499

Gnomad OTH AF: 0.0509

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

GnomAD4 genome AF: 0.0352 AC: 5279 AN: 150104 Hom.: 137 Cov.: 32 AF XY: 0.0343 AC XY: 2510 AN XY: 73110

Gnomad4 AFR AF: 0.00817

Gnomad4 AMR AF: 0.0377

Gnomad4 ASJ AF: 0.0604

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.0284

Gnomad4 FIN AF: 0.0510

Gnomad4 NFE AF: 0.0499

Gnomad4 OTH AF: 0.0507

Alfa AF: 0.0438 Hom.: 83

Bravo AF: 0.0327

Asia WGS AF: 0.0120 AC: 45 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.4
DANN	Benign	0.18

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: rs10489753; hg19: chr1-186108672;