rs2146098

Variant names:

• chr1-186121238-A-G
• rs2146098
• NM_031935.3:c.12229+1093A>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.12229+1093A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 151,976 control chromosomes in the GnomAD database, including 19,983 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 0.49 (19983 hom., cov: 32)
• Consequence: HMCN1 NM_031935.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 8 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMCN1	NM_031935.3	c.12229+1093A>G		intron_variant	Intron 80 of 106	ENST00000271588.9	NP_114141.2
HMCN1	XM_011510038.4	c.12229+1093A>G		intron_variant	Intron 80 of 105		XP_011508340.1
HMCN1	XM_017002437.2	c.10252+1093A>G		intron_variant	Intron 69 of 95		XP_016857926.1
HMCN1	XM_047431608.1	c.8053+1093A>G		intron_variant	Intron 57 of 83		XP_047287564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMCN1	ENST00000271588.9	c.12229+1093A>G		intron_variant	Intron 80 of 106	1	NM_031935.3	ENSP00000271588.4

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74241 AN: 151858 Hom.: 19912 Cov.: 32

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.448

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

GnomAD4 genome AF: 0.489 AC: 74371 AN: 151976 Hom.: 19983 Cov.: 32 AF XY: 0.492 AC XY: 36545 AN XY: 74290

African (AFR) AF: 0.704 AC: 29166 AN: 41452

American (AMR) AF: 0.527 AC: 8038 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1348 AN: 3472

East Asian (EAS) AF: 0.603 AC: 3100 AN: 5142

South Asian (SAS) AF: 0.523 AC: 2525 AN: 4828

European-Finnish (FIN) AF: 0.414 AC: 4370 AN: 10552

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.361 AC: 24542 AN: 67950

Other (OTH) AF: 0.455 AC: 960 AN: 2108

Alfa AF: 0.413 Hom.: 20334

Bravo AF: 0.509

Asia WGS AF: 0.584 AC: 2032 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.20
DANN	Benign	0.39
PhyloP100		-1.4
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: rs2146098; hg19: chr1-186090370;