chr17-39917587-G-A

Variant names:

• chr17-39917587-G-A
• rs77749396
• NM_001165958.2:c.-14-257C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001165958.2(GSDMB):​c.-14-257C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.000057 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: GSDMB NM_001165958.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 6 publications found

Genes affected

GSDMB (HGNC:23690): (gasdermin B) This gene encodes a member of the gasdermin-domain containing protein family. Other gasdermin-family genes are implicated in the regulation of apoptosis in epithelial cells, and are linked to cancer. Alternative splicing and the use of alternative promoters results in multiple transcript variants. Additional variants have been described, but they are candidates for nonsense-mediated mRNA decay (NMD) and are unlikely to be protein-coding. [provided by RefSeq, Nov 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSDMB	NM_001165958.2	c.-14-257C>T		intron_variant	Intron 1 of 10	ENST00000418519.6	NP_001159430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSDMB	ENST00000418519.6	c.-14-257C>T		intron_variant	Intron 1 of 10	5	NM_001165958.2	ENSP00000415049.1

Frequencies

GnomAD3 genomes AF: 0.0000569 AC: 2 AN: 35140 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00243

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000511

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000133 AC: 9 AN: 67430 Hom.: 0 Cov.: 0 AF XY: 0.000113 AC XY: 4 AN XY: 35262

African (AFR) AF: 0.00 AC: 0 AN: 1132

American (AMR) AF: 0.00 AC: 0 AN: 2126

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1710

East Asian (EAS) AF: 0.00207 AC: 2 AN: 966

South Asian (SAS) AF: 0.000506 AC: 4 AN: 7902

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4540

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 220

European-Non Finnish (NFE) AF: 0.0000664 AC: 3 AN: 45194

Other (OTH) AF: 0.00 AC: 0 AN: 3640

GnomAD4 genome AF: 0.0000569 AC: 2 AN: 35140 Hom.: 0 Cov.: 0 AF XY: 0.0000580 AC XY: 1 AN XY: 17246

African (AFR) AF: 0.00 AC: 0 AN: 5748

American (AMR) AF: 0.00 AC: 0 AN: 3024

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 768

East Asian (EAS) AF: 0.00243 AC: 1 AN: 412

South Asian (SAS) AF: 0.00 AC: 0 AN: 980

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3704

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 46

European-Non Finnish (NFE) AF: 0.0000511 AC: 1 AN: 19586

Other (OTH) AF: 0.00 AC: 0 AN: 440

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.61
PhyloP100		-1.3
PromoterAI		0.0099	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Other links and lift over

dbSNP: rs77749396; hg19: chr17-38073840;