chr1-186140693-T-A

Variant names:

• chr1-186140693-T-A
• rs4650695
• NM_031935.3:c.13924+2721T>A

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+2721T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 151,932 control chromosomes in the GnomAD database, including 13,370 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 (13370 hom., cov: 32)
• Consequence: HMCN1 NM_031935.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850
• Publications: 2 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: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine

ENSG00000294274 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.56 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMCN1	NM_031935.3	MANE Select	c.13924+2721T>A		intron	N/A	NP_114141.2	Q96RW7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMCN1	ENST00000271588.9	TSL:1 MANE Select	c.13924+2721T>A		intron	N/A	ENSP00000271588.4	Q96RW7-1
	ENSG00000294274	ENST00000722342.1		n.239-2760A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62253 AN: 151814 Hom.: 13328 Cov.: 32

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.410 AC: 62333 AN: 151932 Hom.: 13370 Cov.: 32 AF XY: 0.414 AC XY: 30749 AN XY: 74250

African (AFR) AF: 0.485 AC: 20096 AN: 41446

American (AMR) AF: 0.494 AC: 7540 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1191 AN: 3464

East Asian (EAS) AF: 0.578 AC: 2978 AN: 5154

South Asian (SAS) AF: 0.449 AC: 2165 AN: 4818

European-Finnish (FIN) AF: 0.400 AC: 4222 AN: 10558

Middle Eastern (MID) AF: 0.312 AC: 91 AN: 292

European-Non Finnish (NFE) AF: 0.339 AC: 23032 AN: 67938

Other (OTH) AF: 0.389 AC: 817 AN: 2102

Alfa AF: 0.255 Hom.: 614

Bravo AF: 0.424

Asia WGS AF: 0.500 AC: 1738 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.8
DANN	Benign	0.84
PhyloP100		-0.085
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: rs4650695; hg19: chr1-186109825;