1-186141945-G-C

Variant names:

• chr1-186141945-G-C
• rs2224575
• NM_031935.3:c.13925-2228G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000271588.9(HMCN1):​c.13925-2228G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 151,906 control chromosomes in the GnomAD database, including 21,203 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 0.50 (21203 hom., cov: 31)
• Consequence: HMCN1 ENST00000271588.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.193
• 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)

ENSG00000294274 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000271588.9. 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.13925-2228G>C		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.13925-2228G>C		intron	N/A	ENSP00000271588.4
	ENSG00000294274	ENST00000722342.1		n.239-4012C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75510 AN: 151790 Hom.: 21135 Cov.: 31

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.449

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

GnomAD4 genome AF: 0.498 AC: 75630 AN: 151906 Hom.: 21203 Cov.: 31 AF XY: 0.500 AC XY: 37098 AN XY: 74214

African (AFR) AF: 0.758 AC: 31438 AN: 41450

American (AMR) AF: 0.530 AC: 8071 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1243 AN: 3466

East Asian (EAS) AF: 0.587 AC: 3023 AN: 5152

South Asian (SAS) AF: 0.455 AC: 2198 AN: 4826

European-Finnish (FIN) AF: 0.414 AC: 4365 AN: 10532

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.354 AC: 24016 AN: 67926

Other (OTH) AF: 0.456 AC: 965 AN: 2116

Alfa AF: 0.294 Hom.: 764

Bravo AF: 0.522

Asia WGS AF: 0.534 AC: 1859 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	0.96
DANN	Benign	0.39
PhyloP100		-0.19
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: rs2224575; hg19: chr1-186111077;