rs10489717

Variant names:

• chr1-185954443-G-A
• rs10489717
• NM_031935.3:c.1829-8075G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-185954443-G-A
• chr1-185954443-G-C

Variant summary

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

The NM_031935.3(HMCN1):​c.1829-8075G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 151,876 control chromosomes in the GnomAD database, including 2,043 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 0.10 (2043 hom., cov: 31)
• Consequence: HMCN1 NM_031935.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.726
• 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMCN1	NM_031935.3	c.1829-8075G>A		intron_variant	Intron 11 of 106	ENST00000271588.9	NP_114141.2
HMCN1	XM_011510038.4	c.1829-8075G>A		intron_variant	Intron 11 of 105		XP_011508340.1
HMCN1	XM_024450118.2	c.1829-8075G>A		intron_variant	Intron 11 of 66		XP_024305886.1
HMCN1	XM_011510041.4	c.1829-8075G>A		intron_variant	Intron 11 of 60		XP_011508343.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMCN1	ENST00000271588.9	c.1829-8075G>A		intron_variant	Intron 11 of 106	1	NM_031935.3	ENSP00000271588.4

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15233 AN: 151758 Hom.: 2015 Cov.: 31

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.0440

Gnomad AMR AF: 0.0426

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.00638

Gnomad SAS AF: 0.0473

Gnomad FIN AF: 0.0129

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0183

Gnomad OTH AF: 0.0905

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

GnomAD4 genome AF: 0.101 AC: 15311 AN: 151876 Hom.: 2043 Cov.: 31 AF XY: 0.0970 AC XY: 7201 AN XY: 74230

African (AFR) AF: 0.308 AC: 12714 AN: 41336

American (AMR) AF: 0.0426 AC: 650 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0167 AC: 58 AN: 3468

East Asian (EAS) AF: 0.00640 AC: 33 AN: 5160

South Asian (SAS) AF: 0.0471 AC: 225 AN: 4778

European-Finnish (FIN) AF: 0.0129 AC: 136 AN: 10578

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0183 AC: 1245 AN: 67970

Other (OTH) AF: 0.0905 AC: 191 AN: 2110

Alfa AF: 0.0301 Hom.: 441

Bravo AF: 0.111

Asia WGS AF: 0.0700 AC: 243 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.51
DANN	Benign	0.44
PhyloP100		-0.73
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: rs10489717; hg19: chr1-185923575;