1-186185636-T-C

Variant names:

• chr1-186185636-T-C
• rs10489751
• NM_031935.3:c.16415-2247T>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.16415-2247T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0279 in 152,376 control chromosomes in the GnomAD database, including 154 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 0.028 (154 hom., cov: 33)
• Consequence: HMCN1 NM_031935.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.222
• 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: 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0952 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.16415-2247T>C		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.16415-2247T>C		intron	N/A	ENSP00000271588.4	Q96RW7-1
	HMCN1	ENST00000414277.1	TSL:3	c.440-2247T>C		intron	N/A	ENSP00000406205.1	Q5TCP6
	ENSG00000294274	ENST00000722342.1		n.238+36120A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0278 AC: 4239 AN: 152258 Hom.: 151 Cov.: 33

Gnomad AFR AF: 0.00916

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0986

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.0547

Gnomad SAS AF: 0.0375

Gnomad FIN AF: 0.0462

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0187

Gnomad OTH AF: 0.0320

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

GnomAD4 genome AF: 0.0279 AC: 4253 AN: 152376 Hom.: 154 Cov.: 33 AF XY: 0.0312 AC XY: 2328 AN XY: 74508

African (AFR) AF: 0.00914 AC: 380 AN: 41596

American (AMR) AF: 0.0993 AC: 1520 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 39 AN: 3468

East Asian (EAS) AF: 0.0549 AC: 285 AN: 5194

South Asian (SAS) AF: 0.0381 AC: 184 AN: 4826

European-Finnish (FIN) AF: 0.0462 AC: 491 AN: 10624

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0187 AC: 1274 AN: 68042

Other (OTH) AF: 0.0317 AC: 67 AN: 2114

Alfa AF: 0.0211 Hom.: 146

Bravo AF: 0.0343

Asia WGS AF: 0.0430 AC: 149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.38
DANN	Benign	0.68
PhyloP100		-0.22
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: rs10489751; hg19: chr1-186154768;