1-185897712-G-A

Position:

• chr1-185897712-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.622-11625G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 151,810 control chromosomes in the GnomAD database, including 27,483 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 0.57 (27483 hom., cov: 31)
• Consequence: HMCN1 NM_031935.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.470

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMCN1	NM_031935.3	c.622-11625G>A		intron_variant		ENST00000271588.9	NP_114141.2
HMCN1	XM_011510038.4	c.622-11625G>A		intron_variant			XP_011508340.1
HMCN1	XM_024450118.2	c.622-11625G>A		intron_variant			XP_024305886.1
HMCN1	XM_011510041.4	c.622-11625G>A		intron_variant			XP_011508343.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMCN1	ENST00000271588.9	c.622-11625G>A		intron_variant		1	NM_031935.3	ENSP00000271588.4

Frequencies

GnomAD3 genomes AF: 0.565 AC: 85776 AN: 151690 Hom.: 27408 Cov.: 31

Gnomad AFR AF: 0.892

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.513

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

GnomAD4 genome AF: 0.566 AC: 85910 AN: 151810 Hom.: 27483 Cov.: 31 AF XY: 0.562 AC XY: 41709 AN XY: 74150

Gnomad4 AFR AF: 0.892

Gnomad4 AMR AF: 0.427

Gnomad4 ASJ AF: 0.436

Gnomad4 EAS AF: 0.487

Gnomad4 SAS AF: 0.506

Gnomad4 FIN AF: 0.454

Gnomad4 NFE AF: 0.436

Gnomad4 OTH AF: 0.519

Alfa AF: 0.457 Hom.: 9034

Bravo AF: 0.575

Asia WGS AF: 0.602 AC: 2097 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.39
DANN	Benign	0.43

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: rs1475113; hg19: chr1-185866844;