Genetic Variant GJB5:c.-91A>G (chr1-34755129-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_005268.4(GJB5):c.-91A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 152,638 control chromosomes in the GnomAD database, including 20,947 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 0.50 ( 20914 hom., cov: 34)

Exomes 𝑓: 0.38 ( 33 hom. )

Consequence

GJB5
NM_005268.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.357

Publications

11 publications found

Variant links:

Genes affected

GJB5 (HGNC:4287): (gap junction protein beta 5) This gene encodes a member of the beta-type (group I) connexin family. The encoded protein is a gap junction protein involved in intercellular communication related to epidermal differentiation and environmental sensing. This gene has been linked to non-small cell lung cancer. [provided by RefSeq, Nov 2012]

GJB5 links:

SMIM12 (HGNC:25154): (small integral membrane protein 12) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SMIM12 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=-0.77).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GJB5	NM_005268.4 link	c.-91A>G		5_prime_UTR_variant	Exon 1 of 2	ENST00000338513.1	NP_005259.1	O95377A0A654IE64
GJB5	XM_005270751.4 link	c.-88A>G		5_prime_UTR_variant	Exon 1 of 2		XP_005270808.1	O95377A0A654IE64

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GJB5	ENST00000338513.1 link	c.-91A>G		5_prime_UTR_variant	Exon 1 of 2	1	NM_005268.4	ENSP00000340811.1		O95377
SMIM12	ENST00000426886.1 link	n.208-36720T>C		intron_variant	Intron 2 of 4	1		ENSP00000429902.1		E5RH51

Frequencies

GnomAD3 genomes

AF:

0.496

AC:

75416

AN:

152098

Hom.:

20881

Cov.:

show subpopulations

Gnomad AFR

AF:

0.758

Gnomad AMI

AF:

0.520

Gnomad AMR

AF:

0.412

Gnomad ASJ

AF:

0.403

Gnomad EAS

AF:

0.525

Gnomad SAS

AF:

0.411

Gnomad FIN

AF:

0.335

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.389

Gnomad OTH

AF:

0.478

GnomAD4 exome

AF:

0.377

AC:

159

AN:

422

Hom.:

Cov.:

AF XY:

0.377

AC XY:

122

AN XY:

324

show subpopulations

African (AFR)

AF:

0.929

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

AN:

East Asian (EAS)

AF:

0.333

AC:

AN:

South Asian (SAS)

AF:

0.167

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.357

AC:

130

AN:

364

Other (OTH)

AF:

0.429

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.526

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:

0.496

AC:

75498

AN:

152216

Hom.:

20914

Cov.:

AF XY:

0.492

AC XY:

36640

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.758

AC:

31493

AN:

41544

American (AMR)

AF:

0.411

AC:

6288

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.403

AC:

1399

AN:

3472

East Asian (EAS)

AF:

0.527

AC:

2723

AN:

5170

South Asian (SAS)

AF:

0.412

AC:

1987

AN:

4824

European-Finnish (FIN)

AF:

0.335

AC:

3551

AN:

10594

Middle Eastern (MID)

AF:

0.527

AC:

155

AN:

294

European-Non Finnish (NFE)

AF:

0.389

AC:

26427

AN:

67990

Other (OTH)

AF:

0.474

AC:

1001

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1822

3645

5467

7290

9112

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

648

1296

1944

2592

3240

<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:

0.432

Hom.:

7761

Bravo

AF:

0.514

Asia WGS

AF:

0.450

AC:

1563

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

-0.36

PromoterAI

-0.033

Neutral

(source)

Mutation Taster

=300/0

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