Genetic Variant HMCN1:c.16415-2247T>C (chr1-186185636-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.222

Publications

1 publications found

Variant links:

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)

HMCN1 links:

ENSG00000294274 (HGNC:):

ENSG00000294274 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMCN1	NM_031935.3 link	c.16415-2247T>C		intron_variant	Intron 105 of 106	ENST00000271588.9	NP_114141.2	Q96RW7-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
HMCN1	ENST00000271588.9 link	c.16415-2247T>C	intron_variant	Intron 105 of 106	1	NM_031935.3	ENSP00000271588.4	Q96RW7-1
HMCN1	ENST00000414277.1 link	c.440-2247T>C	intron_variant	Intron 4 of 5	3		ENSP00000406205.1	Q5TCP6
ENSG00000294274	ENST00000722342.1 link	n.238+36120A>G	intron_variant	Intron 1 of 3
ENSG00000294274	ENST00000722343.1 link	n.253-381A>G	intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.0278

AC:

4239

AN:

152258

Hom.:

151

Cov.:

show subpopulations

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.:

AF XY:

0.0312

AC XY:

2328

AN XY:

74508

show subpopulations

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:

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0187

AC:

1274

AN:

68042

Other (OTH)

AF:

0.0317

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

207

413

620

826

1033

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.38

(source)

DANN

Benign

0.68

PhyloP100

-0.22

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over