chr22-17750138-CC-TG

Variant names:

• chr22-17750138-CC-TG
• ENST00000317361.11:c.116_117delGGinsCA
• BID p.Arg39Pro

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_197966.3(BID):​c.116_117delGGinsCA​(p.Arg39Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R39G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: BID NM_197966.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.803
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_197966.3. 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
	BID	NM_001196.4	MANE Select	c.-23_-22delGGinsCA		5_prime_UTR	Exon 2 of 6	NP_001187.1	A8ASI8
	BID	NM_197966.3		c.116_117delGGinsCA	p.Arg39Pro	missense	N/A	NP_932070.1	P55957-2
	BID	NM_001244567.1		c.-23_-22delGGinsCA		5_prime_UTR	Exon 2 of 6	NP_001231496.1	A8ASI8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BID	ENST00000317361.11	TSL:1	c.116_117delGGinsCA	p.Arg39Pro	missense	N/A	ENSP00000318822.7	P55957-2
	BID	ENST00000622694.5	TSL:1 MANE Select	c.-23_-22delGGinsCA		5_prime_UTR	Exon 2 of 6	ENSP00000480414.1	P55957-1
	BID	ENST00000551952.5	TSL:1	c.-23_-22delGGinsCA		5_prime_UTR	Exon 2 of 6	ENSP00000449236.1	P55957-1

Frequencies

GnomAD3 genomes Cov.: 34

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.80

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr22-18232904;