rs10489718

Positions:

• chr1-185957447-A-G

Variant summary

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

The NM_031935.3(HMCN1):​c.1829-5071A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0595 in 152,140 control chromosomes in the GnomAD database, including 646 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 0.060 (646 hom., cov: 32)
• Consequence: HMCN1 NM_031935.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMCN1	NM_031935.3	c.1829-5071A>G		intron_variant		ENST00000271588.9	NP_114141.2
HMCN1	XM_011510038.4	c.1829-5071A>G		intron_variant			XP_011508340.1
HMCN1	XM_011510041.4	c.1829-5071A>G		intron_variant			XP_011508343.1
HMCN1	XM_024450118.2	c.1829-5071A>G		intron_variant			XP_024305886.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMCN1	ENST00000271588.9	c.1829-5071A>G		intron_variant		1	NM_031935.3	ENSP00000271588	P1
HMCN1	ENST00000485744.5	n.72+307A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0592 AC: 8999 AN: 152022 Hom.: 629 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0290

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.00456

Gnomad FIN AF: 0.0127

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0180

Gnomad OTH AF: 0.0589

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

GnomAD4 genome AF: 0.0595 AC: 9053 AN: 152140 Hom.: 646 Cov.: 32 AF XY: 0.0569 AC XY: 4232 AN XY: 74410

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.0291

Gnomad4 ASJ AF: 0.0147

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.00436

Gnomad4 FIN AF: 0.0127

Gnomad4 NFE AF: 0.0180

Gnomad4 OTH AF: 0.0592

Alfa AF: 0.0393 Hom.: 38

Bravo AF: 0.0657

Asia WGS AF: 0.0270 AC: 93 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.075
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: rs10489718; hg19: chr1-185926579;