rs12080760

Variant names:

• chr1-186140164-G-T
• rs12080760
• NM_031935.3:c.13924+2192G>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.13924+2192G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 151,856 control chromosomes in the GnomAD database, including 17,784 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 0.46 (17784 hom., cov: 31)
• Consequence: HMCN1 NM_031935.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.18
• Publications: 3 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)

ENSG00000294274 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031935.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMCN1	NM_031935.3	MANE Select	c.13924+2192G>T		intron	N/A	NP_114141.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMCN1	ENST00000271588.9	TSL:1 MANE Select	c.13924+2192G>T		intron	N/A	ENSP00000271588.4
	ENSG00000294274	ENST00000722342.1		n.239-2231C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.461 AC: 69978 AN: 151738 Hom.: 17719 Cov.: 31

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.412

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

GnomAD4 genome AF: 0.462 AC: 70101 AN: 151856 Hom.: 17784 Cov.: 31 AF XY: 0.465 AC XY: 34494 AN XY: 74194

African (AFR) AF: 0.665 AC: 27560 AN: 41426

American (AMR) AF: 0.509 AC: 7759 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1197 AN: 3472

East Asian (EAS) AF: 0.576 AC: 2979 AN: 5172

South Asian (SAS) AF: 0.451 AC: 2168 AN: 4810

European-Finnish (FIN) AF: 0.402 AC: 4229 AN: 10510

Middle Eastern (MID) AF: 0.325 AC: 95 AN: 292

European-Non Finnish (NFE) AF: 0.339 AC: 23030 AN: 67904

Other (OTH) AF: 0.418 AC: 883 AN: 2110

Alfa AF: 0.391 Hom.: 23682

Bravo AF: 0.481

Asia WGS AF: 0.513 AC: 1786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.22
DANN	Benign	0.29
PhyloP100		-3.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12080760; hg19: chr1-186109296;