rs10489718

Variant names:

• chr1-185957447-A-G
• rs10489718
• NM_031935.3:c.1829-5071A>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.1829-5071A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0595 in 152,140 control chromosomes in the GnomAD database, including 646 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 0.060 (646 hom., cov: 32)
• Consequence: HMCN1 NM_031935.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17
• 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMCN1	NM_031935.3	c.1829-5071A>G		intron_variant	Intron 11 of 106	ENST00000271588.9	NP_114141.2
HMCN1	XM_011510038.4	c.1829-5071A>G		intron_variant	Intron 11 of 105		XP_011508340.1
HMCN1	XM_024450118.2	c.1829-5071A>G		intron_variant	Intron 11 of 66		XP_024305886.1
HMCN1	XM_011510041.4	c.1829-5071A>G		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.1829-5071A>G		intron_variant	Intron 11 of 106	1	NM_031935.3	ENSP00000271588.4
HMCN1	ENST00000485744.5	n.72+307A>G		intron_variant	Intron 1 of 12	2

Frequencies

GnomAD3 genomes AF: 0.0592 AC: 8999 AN: 152022 Hom.: 629 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0290

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.00456

Gnomad FIN AF: 0.0127

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0180

Gnomad OTH AF: 0.0589

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

GnomAD4 genome AF: 0.0595 AC: 9053 AN: 152140 Hom.: 646 Cov.: 32 AF XY: 0.0569 AC XY: 4232 AN XY: 74410

African (AFR) AF: 0.168 AC: 6986 AN: 41466

American (AMR) AF: 0.0291 AC: 444 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 51 AN: 3472

East Asian (EAS) AF: 0.00232 AC: 12 AN: 5182

South Asian (SAS) AF: 0.00436 AC: 21 AN: 4820

European-Finnish (FIN) AF: 0.0127 AC: 135 AN: 10598

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0180 AC: 1221 AN: 68010

Other (OTH) AF: 0.0592 AC: 125 AN: 2110

Alfa AF: 0.0453 Hom.: 54

Bravo AF: 0.0657

Asia WGS AF: 0.0270 AC: 93 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.075
DANN	Benign	0.44
PhyloP100		-2.2
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: rs10489718; hg19: chr1-185926579;