17-39912261-T-A

Variant names:

• chr17-39912261-T-A
• rs1011082
• NM_001165958.2:c.407+65A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001165958.2(GSDMB):​c.407+65A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000218 in 1,193,980 control chromosomes in the GnomAD database, including 1 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 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000024 (1 hom.)
• Consequence: GSDMB NM_001165958.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.833
• Publications: 23 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSDMB	NM_001165958.2	c.407+65A>T		intron_variant	Intron 3 of 10	ENST00000418519.6	NP_001159430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSDMB	ENST00000418519.6	c.407+65A>T		intron_variant	Intron 3 of 10	5	NM_001165958.2	ENSP00000415049.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151980 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000240 AC: 25 AN: 1042000 Hom.: 1 AF XY: 0.0000245 AC XY: 13 AN XY: 530910

African (AFR) AF: 0.00 AC: 0 AN: 23508

American (AMR) AF: 0.0000329 AC: 1 AN: 30402

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20824

East Asian (EAS) AF: 0.00 AC: 0 AN: 36586

South Asian (SAS) AF: 0.00 AC: 0 AN: 68972

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51700

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3328

European-Non Finnish (NFE) AF: 0.0000315 AC: 24 AN: 761068

Other (OTH) AF: 0.00 AC: 0 AN: 45612

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151980 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74218

African (AFR) AF: 0.0000242 AC: 1 AN: 41360

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 7648

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.61
PhyloP100		-0.83

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

Other links and lift over

dbSNP: rs1011082; hg19: chr17-38068514;