NM_031935.3:c.13312+1005T>G

Variant names:

• chr1-186133414-T-G
• rs721153
• NM_031935.3:c.13312+1005T>G

Variant summary

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

The NM_031935.3(HMCN1):​c.13312+1005T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 152,002 control chromosomes in the GnomAD database, including 13,459 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 0.41 (13459 hom., cov: 32)
• Consequence: HMCN1 NM_031935.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0910
• Publications: 0 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMCN1	NM_031935.3	c.13312+1005T>G		intron_variant	Intron 86 of 106	ENST00000271588.9	NP_114141.2
HMCN1	XM_011510038.4	c.13312+1005T>G		intron_variant	Intron 86 of 105		XP_011508340.1
HMCN1	XM_017002437.2	c.11335+1005T>G		intron_variant	Intron 75 of 95		XP_016857926.1
HMCN1	XM_047431608.1	c.9136+1005T>G		intron_variant	Intron 63 of 83		XP_047287564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMCN1	ENST00000271588.9	c.13312+1005T>G		intron_variant	Intron 86 of 106	1	NM_031935.3	ENSP00000271588.4
ENSG00000294274	ENST00000722342.1	n.588+2880A>C		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62453 AN: 151882 Hom.: 13416 Cov.: 32

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.384

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

GnomAD4 genome AF: 0.411 AC: 62530 AN: 152002 Hom.: 13459 Cov.: 32 AF XY: 0.415 AC XY: 30847 AN XY: 74294

African (AFR) AF: 0.487 AC: 20162 AN: 41440

American (AMR) AF: 0.495 AC: 7548 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1194 AN: 3464

East Asian (EAS) AF: 0.579 AC: 2984 AN: 5158

South Asian (SAS) AF: 0.451 AC: 2172 AN: 4818

European-Finnish (FIN) AF: 0.401 AC: 4241 AN: 10574

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.340 AC: 23110 AN: 67974

Other (OTH) AF: 0.390 AC: 826 AN: 2116

Alfa AF: 0.298 Hom.: 1066

Bravo AF: 0.425

Asia WGS AF: 0.499 AC: 1737 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.32
PhyloP100		0.091
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: rs721153; hg19: chr1-186102546;