rs2891230

Positions:

• chr1-186119940-G-A

Variant summary

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

The NM_031935.3(HMCN1):​c.12094+58G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 1,613,322 control chromosomes in the GnomAD database, including 98,937 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 0.34 (9092 hom., cov: 32)
  • Exomes 𝑓: 0.34 (89845 hom.)
• Consequence: HMCN1 NM_031935.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.11

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMCN1	NM_031935.3	c.12094+58G>A		intron_variant		ENST00000271588.9	NP_114141.2
HMCN1	XM_011510038.4	c.12094+58G>A		intron_variant			XP_011508340.1
HMCN1	XM_017002437.2	c.10117+58G>A		intron_variant			XP_016857926.1
HMCN1	XM_047431608.1	c.7918+58G>A		intron_variant			XP_047287564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMCN1	ENST00000271588.9	c.12094+58G>A		intron_variant		1	NM_031935.3	ENSP00000271588.4

Frequencies

GnomAD3 genomes AF: 0.336 AC: 50999 AN: 151704 Hom.: 9060 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.337

GnomAD4 exome AF: 0.345 AC: 504216 AN: 1461508 Hom.: 89845 Cov.: 37 AF XY: 0.346 AC XY: 251919 AN XY: 727062

Gnomad4 AFR exome AF: 0.260

Gnomad4 AMR exome AF: 0.557

Gnomad4 ASJ exome AF: 0.333

Gnomad4 EAS exome AF: 0.521

Gnomad4 SAS exome AF: 0.402

Gnomad4 FIN exome AF: 0.378

Gnomad4 NFE exome AF: 0.327

Gnomad4 OTH exome AF: 0.349

GnomAD4 genome AF: 0.336 AC: 51060 AN: 151814 Hom.: 9092 Cov.: 32 AF XY: 0.342 AC XY: 25369 AN XY: 74166

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.327

Gnomad4 EAS AF: 0.547

Gnomad4 SAS AF: 0.415

Gnomad4 FIN AF: 0.386

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.345

Alfa AF: 0.353 Hom.: 1564

Bravo AF: 0.342

Asia WGS AF: 0.465 AC: 1616 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.4
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2891230; hg19: chr1-186089072; COSMIC: COSV54917719;