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:

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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=-0.77).

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005268.4. 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
	GJB5	NM_005268.4	MANE Select	c.-91A>G		5_prime_UTR	Exon 1 of 2	NP_005259.1	O95377

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GJB5	ENST00000338513.1	TSL:1 MANE Select	c.-91A>G	5_prime_UTR	Exon 1 of 2	ENSP00000340811.1	O95377
SMIM12	ENST00000426886.1	TSL:1	n.208-36720T>C	intron	N/A	ENSP00000429902.1	E5RH51
GJB5	ENST00000863284.1		c.-88A>G	5_prime_UTR	Exon 1 of 2	ENSP00000533343.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over