1-186143373-A-G

Variant names:

• chr1-186143373-A-G
• rs6664918
• NM_031935.3:c.13925-800A>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.13925-800A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 151,918 control chromosomes in the GnomAD database, including 13,785 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 0.42 (13785 hom., cov: 32)
• Consequence: HMCN1 NM_031935.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.324
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMCN1	NM_031935.3	c.13925-800A>G		intron_variant	Intron 89 of 106	ENST00000271588.9	NP_114141.2
HMCN1	XM_011510038.4	c.13925-800A>G		intron_variant	Intron 89 of 105		XP_011508340.1
HMCN1	XM_017002437.2	c.11948-800A>G		intron_variant	Intron 78 of 95		XP_016857926.1
HMCN1	XM_047431608.1	c.9749-800A>G		intron_variant	Intron 66 of 83		XP_047287564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMCN1	ENST00000271588.9	c.13925-800A>G		intron_variant	Intron 89 of 106	1	NM_031935.3	ENSP00000271588.4
ENSG00000294274	ENST00000722342.1	n.239-5440T>C		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63071 AN: 151798 Hom.: 13741 Cov.: 32

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.321

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.387

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

GnomAD4 genome AF: 0.416 AC: 63155 AN: 151918 Hom.: 13785 Cov.: 32 AF XY: 0.420 AC XY: 31142 AN XY: 74232

African (AFR) AF: 0.501 AC: 20759 AN: 41442

American (AMR) AF: 0.496 AC: 7569 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1193 AN: 3466

East Asian (EAS) AF: 0.585 AC: 3014 AN: 5154

South Asian (SAS) AF: 0.450 AC: 2168 AN: 4816

European-Finnish (FIN) AF: 0.402 AC: 4230 AN: 10530

Middle Eastern (MID) AF: 0.318 AC: 93 AN: 292

European-Non Finnish (NFE) AF: 0.340 AC: 23098 AN: 67940

Other (OTH) AF: 0.393 AC: 831 AN: 2114

Alfa AF: 0.383 Hom.: 2848

Bravo AF: 0.430

Asia WGS AF: 0.503 AC: 1752 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.4
DANN	Benign	0.76
PhyloP100		0.32
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: rs6664918; hg19: chr1-186112505;