rs10489717

chr1-185954443-G-Achr1-185954443-G-C

Variant summary

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

The NM_031935.3(HMCN1):c.1829-8075G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 151,876 control chromosomes in the GnomAD database, including 2,043 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 0.10 (2043 hom., cov: 31)
• Consequence: HMCN1 NM_031935.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.726

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMCN1	NM_031935.3	c.1829-8075G>A		intron_variant		ENST00000271588.9
HMCN1	XM_011510038.4	c.1829-8075G>A		intron_variant
HMCN1	XM_011510041.4	c.1829-8075G>A		intron_variant
HMCN1	XM_024450118.2	c.1829-8075G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMCN1	ENST00000271588.9	c.1829-8075G>A		intron_variant		1	NM_031935.3	P1

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15233 AN: 151758 Hom.: 2015 Cov.: 31

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.0440

Gnomad AMR AF: 0.0426

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.00638

Gnomad SAS AF: 0.0473

Gnomad FIN AF: 0.0129

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0183

Gnomad OTH AF: 0.0905

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

GnomAD4 genome AF: 0.101 AC: 15311 AN: 151876 Hom.: 2043 Cov.: 31 AF XY: 0.0970 AC XY: 7201 AN XY: 74230

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.0426

Gnomad4 ASJ AF: 0.0167

Gnomad4 EAS AF: 0.00640

Gnomad4 SAS AF: 0.0471

Gnomad4 FIN AF: 0.0129

Gnomad4 NFE AF: 0.0183

Gnomad4 OTH AF: 0.0905

Alfa AF: 0.0318 Hom.: 111

Bravo AF: 0.111

Asia WGS AF: 0.0700 AC: 243 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.51
Dann	Benign	0.44

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: rs10489717; hg19: chr1-185923575;