rs193921043

Variant names:

• chr1-186189762-C-A
• rs193921043
• NM_031935.3:c.16792C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-186189762-C-A
• chr1-186189762-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4 BP6_Moderate

The NM_031935.3(HMCN1):​c.16792C>A​(p.Arg5598Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000205 in 1,461,432 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: HMCN1 NM_031935.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.96
• 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: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine

ENSG00000294274 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.16).
• BP6: Variant 1-186189762-C-A is Benign according to our data. Variant chr1-186189762-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1951654.Status of the report is criteria_provided_single_submitter, 1 stars.

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.16792C>A	p.Arg5598Arg	synonymous	Exon 107 of 107	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.16792C>A	p.Arg5598Arg	synonymous	Exon 107 of 107	ENSP00000271588.4	Q96RW7-1
	ENSG00000294274	ENST00000722342.1		n.238+31994G>T		intron	N/A
	ENSG00000294274	ENST00000722343.1		n.253-4507G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 250408 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000870

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461432 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727010

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.0000671 AC: 3 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53308

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111804

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.16
CADD	Benign	8.0
DANN	Benign	0.69
PhyloP100		5.0
Mutation Taster		=69/31	polymorphism

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: rs193921043; hg19: chr1-186158894;