rs1475113

Variant names:

• chr1-185897712-G-A
• rs1475113
• NM_031935.3:c.622-11625G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-185897712-G-A
• chr1-185897712-G-C
• chr1-185897712-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

HMCN1 Gene-Disease associations (from GenCC):

• age related macular degeneration 1

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Laboratory for Molecular Medicine, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HMCN1	NM_031935.3	c.622-11625G>A		intron_variant	Intron 4 of 106	ENST00000271588.9	NP_114141.2
HMCN1	XM_011510038.4	c.622-11625G>A		intron_variant	Intron 4 of 105		XP_011508340.1
HMCN1	XM_024450118.2	c.622-11625G>A		intron_variant	Intron 4 of 66		XP_024305886.1
HMCN1	XM_011510041.4	c.622-11625G>A		intron_variant	Intron 4 of 60		XP_011508343.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMCN1	ENST00000271588.9	c.622-11625G>A		intron_variant	Intron 4 of 106	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

African (AFR) AF: 0.892 AC: 36962 AN: 41440

American (AMR) AF: 0.427 AC: 6521 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1509 AN: 3462

East Asian (EAS) AF: 0.487 AC: 2504 AN: 5146

South Asian (SAS) AF: 0.506 AC: 2439 AN: 4822

European-Finnish (FIN) AF: 0.454 AC: 4769 AN: 10494

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.436 AC: 29603 AN: 67882

Other (OTH) AF: 0.519 AC: 1093 AN: 2106

Alfa AF: 0.459 Hom.: 12452

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
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1475113; hg19: chr1-185866844;