chr1-186023526-A-C

Position:

• chr1-186023526-A-C

Variant summary

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

The NM_031935.3(HMCN1):​c.5749+373A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 151,992 control chromosomes in the GnomAD database, including 33,787 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 0.65 (33787 hom., cov: 31)
• Consequence: HMCN1 NM_031935.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMCN1	NM_031935.3	c.5749+373A>C		intron_variant		ENST00000271588.9	NP_114141.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMCN1	ENST00000271588.9	c.5749+373A>C		intron_variant		1	NM_031935.3	ENSP00000271588	P1

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98350 AN: 151872 Hom.: 33724 Cov.: 31

Gnomad AFR AF: 0.898

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.614

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.626

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

GnomAD4 genome AF: 0.648 AC: 98476 AN: 151992 Hom.: 33787 Cov.: 31 AF XY: 0.643 AC XY: 47763 AN XY: 74272

Gnomad4 AFR AF: 0.898

Gnomad4 AMR AF: 0.590

Gnomad4 ASJ AF: 0.667

Gnomad4 EAS AF: 0.613

Gnomad4 SAS AF: 0.628

Gnomad4 FIN AF: 0.518

Gnomad4 NFE AF: 0.534

Gnomad4 OTH AF: 0.630

Alfa AF: 0.476 Hom.: 1653

Bravo AF: 0.663

Asia WGS AF: 0.665 AC: 2311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.3
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs743137; hg19: chr1-185992658;