Genetic Variant ENSG00000256433:n.161+6G>C (chr12-6394334-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000541888.2(ENSG00000256433):n.161+6G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,232 control chromosomes in the GnomAD database, including 2,490 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 0.17 ( 2488 hom., cov: 32)

Exomes 𝑓: 0.22 ( 2 hom. )

Consequence

ENSG00000256433
ENST00000541888.2 splice_region, intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.107

Publications

28 publications found

Variant links:

Genes affected

ENSG00000256433 (HGNC:):

ENSG00000256433 links:

Genome browser will be placed here

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=-0.89).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000256433	ENST00000541888.2 link	n.161+6G>C		splice_region_variant, intron_variant	Intron 2 of 2	5
ENSG00000256433	ENST00000663143.1 link	n.189+6G>C		splice_region_variant, intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.166

AC:

25156

AN:

151976

Hom.:

2481

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0785

Gnomad AMI

AF:

0.157

Gnomad AMR

AF:

0.308

Gnomad ASJ

AF:

0.144

Gnomad EAS

AF:

0.0418

Gnomad SAS

AF:

0.125

Gnomad FIN

AF:

0.207

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.194

Gnomad OTH

AF:

0.167

GnomAD4 exome

AF:

0.217

AC:

AN:

138

Hom.:

Cov.:

AF XY:

0.236

AC XY:

AN XY:

106

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.167

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.0714

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.225

AC:

AN:

102

Other (OTH)

AF:

0.333

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.166

AC:

25184

AN:

152094

Hom.:

2488

Cov.:

AF XY:

0.167

AC XY:

12423

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.0785

AC:

3255

AN:

41482

American (AMR)

AF:

0.309

AC:

4711

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.144

AC:

498

AN:

3468

East Asian (EAS)

AF:

0.0415

AC:

215

AN:

5184

South Asian (SAS)

AF:

0.127

AC:

610

AN:

4820

European-Finnish (FIN)

AF:

0.207

AC:

2196

AN:

10588

Middle Eastern (MID)

AF:

0.170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.194

AC:

13158

AN:

67966

Other (OTH)

AF:

0.165

AC:

348

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1016

2032

3048

4064

5080

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

278

556

834

1112

1390

<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:

0.189

Hom.:

388

Bravo

AF:

0.171

Asia WGS

AF:

0.0760

AC:

266

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.3

(source)

DANN

Benign

0.70

PhyloP100

-0.11

Splicing

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over