Genetic Variant NM_001196.4:c.*136A>G (chr22-17735444-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_001196.4(BID):c.*136A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0389 in 920,664 control chromosomes in the GnomAD database, including 875 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 0.036 ( 108 hom., cov: 33)

Exomes 𝑓: 0.039 ( 767 hom. )

Consequence

BID
NM_001196.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.46

Publications

11 publications found

Variant links:

Genes affected

BID (HGNC:1050): (BH3 interacting domain death agonist) This gene encodes a death agonist that heterodimerizes with either agonist BAX or antagonist BCL2, and thus regulate apoptosis. The encoded protein is a member of the BCL-2 family of cell death regulators. It is a mediator of mitochondrial damage induced by caspase-8 (CASP8); CASP8 cleaves this encoded protein, and the COOH-terminal part translocates to mitochondria where it triggers cytochrome c release. Multiple alternatively spliced transcript variants have been found. [provided by RefSeq, Aug 2020]

BID 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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0775 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001196.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BID	NM_001196.4	MANE Select	c.*136A>G	3_prime_UTR	Exon 6 of 6	NP_001187.1	A8ASI8
BID	NM_197966.3		c.*136A>G	3_prime_UTR	Exon 6 of 6	NP_932070.1	P55957-2
BID	NM_001244567.1		c.*136A>G	3_prime_UTR	Exon 6 of 6	NP_001231496.1	A8ASI8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BID	ENST00000622694.5	TSL:1 MANE Select	c.*136A>G	3_prime_UTR	Exon 6 of 6	ENSP00000480414.1	P55957-1
BID	ENST00000317361.11	TSL:1	c.*136A>G	3_prime_UTR	Exon 6 of 6	ENSP00000318822.7	P55957-2
BID	ENST00000494097.5	TSL:1	n.2207A>G	non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.0363

AC:

5519

AN:

152202

Hom.:

108

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0375

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0298

Gnomad ASJ

AF:

0.0841

Gnomad EAS

AF:

0.0838

Gnomad SAS

AF:

0.0360

Gnomad FIN

AF:

0.00462

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0358

Gnomad OTH

AF:

0.0406

GnomAD4 exome

AF:

0.0394

AC:

30245

AN:

768344

Hom.:

767

Cov.:

AF XY:

0.0393

AC XY:

15710

AN XY:

399516

show subpopulations

African (AFR)

AF:

0.0381

AC:

695

AN:

18236

American (AMR)

AF:

0.0242

AC:

640

AN:

26438

Ashkenazi Jewish (ASJ)

AF:

0.0828

AC:

1559

AN:

18820

East Asian (EAS)

AF:

0.0986

AC:

3323

AN:

33686

South Asian (SAS)

AF:

0.0382

AC:

2383

AN:

62464

European-Finnish (FIN)

AF:

0.00674

AC:

312

AN:

46266

Middle Eastern (MID)

AF:

0.0549

AC:

234

AN:

4260

European-Non Finnish (NFE)

AF:

0.0374

AC:

19493

AN:

521086

Other (OTH)

AF:

0.0433

AC:

1606

AN:

37088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1415

2830

4245

5660

7075

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

516

1032

1548

2064

2580

<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:

0.0363

AC:

5528

AN:

152320

Hom.:

108

Cov.:

AF XY:

0.0350

AC XY:

2606

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0376

AC:

1565

AN:

41572

American (AMR)

AF:

0.0297

AC:

455

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0841

AC:

292

AN:

3472

East Asian (EAS)

AF:

0.0840

AC:

435

AN:

5180

South Asian (SAS)

AF:

0.0358

AC:

173

AN:

4826

European-Finnish (FIN)

AF:

0.00462

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0358

AC:

2437

AN:

68026

Other (OTH)

AF:

0.0406

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

281

563

844

1126

1407

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<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:

0.0362

Hom.:

Bravo

AF:

0.0386

Asia WGS

AF:

0.0620

AC:

216

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.060

(source)

DANN

Benign

0.39

PhyloP100

-2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over