dbSNP rs440296: GJB7:c.-27-13764C>T (chr6-87298703-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_198568.3(GJB7):c.-27-13764C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 178,976 control chromosomes in the GnomAD database, including 15,146 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 0.41 ( 12881 hom., cov: 32)

Exomes 𝑓: 0.40 ( 2265 hom. )

Consequence

GJB7
NM_198568.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.09

Publications

7 publications found

Variant links:

Genes affected

GJB7 (HGNC:16690): (gap junction protein beta 7) Connexins, such as GJB7, are involved in the formation of gap junctions, intercellular conduits that directly connect the cytoplasms of contacting cells. Each gap junction channel is formed by docking of 2 hemichannels, each of which contains 6 connexin subunits (Sohl et al., 2003 [PubMed 12881038]).[supplied by OMIM, Mar 2008]

GJB7 links:

HSPD1P10 (HGNC:35131): (heat shock protein family D (Hsp60) member 1 pseudogene 10)

HSPD1P10 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=-0.98).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GJB7	NM_198568.3 link	c.-27-13764C>T		intron_variant	Intron 2 of 2	ENST00000525899.6	NP_940970.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GJB7	ENST00000525899.6 link	c.-27-13764C>T		intron_variant	Intron 2 of 2	1	NM_198568.3	ENSP00000435355.1
HSPD1P10	ENST00000404829.2 link	n.-69G>A		upstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.407

AC:

61846

AN:

151910

Hom.:

12868

Cov.:

show subpopulations

Gnomad AFR

AF:

0.402

Gnomad AMI

AF:

0.474

Gnomad AMR

AF:

0.529

Gnomad ASJ

AF:

0.414

Gnomad EAS

AF:

0.460

Gnomad SAS

AF:

0.470

Gnomad FIN

AF:

0.362

Gnomad MID

AF:

0.440

Gnomad NFE

AF:

0.380

Gnomad OTH

AF:

0.412

GnomAD4 exome

AF:

0.397

AC:

10711

AN:

26948

Hom.:

2265

AF XY:

0.403

AC XY:

5618

AN XY:

13932

show subpopulations

African (AFR)

AF:

0.373

AC:

118

AN:

316

American (AMR)

AF:

0.548

AC:

725

AN:

1322

Ashkenazi Jewish (ASJ)

AF:

0.429

AC:

200

AN:

466

East Asian (EAS)

AF:

0.438

AC:

268

AN:

612

South Asian (SAS)

AF:

0.492

AC:

1272

AN:

2586

European-Finnish (FIN)

AF:

0.377

AC:

2178

AN:

5776

Middle Eastern (MID)

AF:

0.490

AC:

AN:

102

European-Non Finnish (NFE)

AF:

0.371

AC:

5335

AN:

14386

Other (OTH)

AF:

0.409

AC:

565

AN:

1382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

306

612

918

1224

1530

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.407

AC:

61905

AN:

152028

Hom.:

12881

Cov.:

AF XY:

0.410

AC XY:

30491

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.402

AC:

16667

AN:

41464

American (AMR)

AF:

0.529

AC:

8084

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.414

AC:

1432

AN:

3462

East Asian (EAS)

AF:

0.460

AC:

2382

AN:

5178

South Asian (SAS)

AF:

0.470

AC:

2265

AN:

4822

European-Finnish (FIN)

AF:

0.362

AC:

3818

AN:

10536

Middle Eastern (MID)

AF:

0.439

AC:

129

AN:

294

European-Non Finnish (NFE)

AF:

0.380

AC:

25828

AN:

67968

Other (OTH)

AF:

0.411

AC:

869

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1889

3777

5666

7554

9443

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

586

1172

1758

2344

2930

<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:

0.388

Hom.:

1502

Bravo

AF:

0.421

Asia WGS

AF:

0.459

AC:

1592

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.95

(source)

DANN

Benign

0.34

PhyloP100

-1.1

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over