chr17-39908152-C-T

Variant names:

• chr17-39908152-C-T
• rs11078927
• NM_001165958.2:c.700+24G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001165958.2(GSDMB):​c.700+24G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 1,358,612 control chromosomes in the GnomAD database, including 119,376 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 0.35 (10770 hom., cov: 30)
  • Exomes 𝑓: 0.42 (108606 hom.)
• Consequence: GSDMB NM_001165958.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341
• Publications: 88 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001165958.2. 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
	GSDMB	NM_001165958.2	MANE Select	c.700+24G>A		intron	N/A	NP_001159430.1	Q8TAX9-4
	GSDMB	NM_001388420.1		c.700+24G>A		intron	N/A	NP_001375349.1	Q8TAX9-4
	GSDMB	NM_001165959.2		c.700+24G>A		intron	N/A	NP_001159431.1	Q8TAX9-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSDMB	ENST00000418519.6	TSL:5 MANE Select	c.700+24G>A		intron	N/A	ENSP00000415049.1	Q8TAX9-4
	GSDMB	ENST00000360317.7	TSL:1	c.700+24G>A		intron	N/A	ENSP00000353465.3	Q8TAX9-4
	GSDMB	ENST00000394179.5	TSL:1	c.661+806G>A		intron	N/A	ENSP00000377733.2	Q8TAX9-3

Frequencies

GnomAD3 genomes AF: 0.349 AC: 52949 AN: 151576 Hom.: 10762 Cov.: 30

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.659

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.350

GnomAD2 exomes AF: 0.399 AC: 62364 AN: 156298 AF XY: 0.404

Gnomad AFR exome AF: 0.124

Gnomad AMR exome AF: 0.329

Gnomad ASJ exome AF: 0.418

Gnomad EAS exome AF: 0.254

Gnomad FIN exome AF: 0.522

Gnomad NFE exome AF: 0.461

Gnomad OTH exome AF: 0.416

GnomAD4 exome AF: 0.418 AC: 504775 AN: 1206918 Hom.: 108606 Cov.: 18 AF XY: 0.418 AC XY: 252822 AN XY: 604168

African (AFR) AF: 0.121 AC: 3546 AN: 29186

American (AMR) AF: 0.335 AC: 11854 AN: 35432

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 9845 AN: 24038

East Asian (EAS) AF: 0.263 AC: 9249 AN: 35180

South Asian (SAS) AF: 0.367 AC: 27796 AN: 75710

European-Finnish (FIN) AF: 0.509 AC: 24989 AN: 49124

Middle Eastern (MID) AF: 0.382 AC: 2045 AN: 5354

European-Non Finnish (NFE) AF: 0.439 AC: 395174 AN: 901034

Other (OTH) AF: 0.391 AC: 20277 AN: 51860

GnomAD4 genome AF: 0.349 AC: 52967 AN: 151694 Hom.: 10770 Cov.: 30 AF XY: 0.352 AC XY: 26110 AN XY: 74076

African (AFR) AF: 0.137 AC: 5672 AN: 41386

American (AMR) AF: 0.372 AC: 5655 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1417 AN: 3468

East Asian (EAS) AF: 0.269 AC: 1388 AN: 5154

South Asian (SAS) AF: 0.370 AC: 1781 AN: 4816

European-Finnish (FIN) AF: 0.519 AC: 5433 AN: 10462

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.445 AC: 30187 AN: 67886

Other (OTH) AF: 0.347 AC: 732 AN: 2108

Alfa AF: 0.414 Hom.: 40783

Bravo AF: 0.322

Asia WGS AF: 0.353 AC: 1228 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.1
DANN	Benign	0.52
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

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: rs11078927; hg19: chr17-38064405; COSMIC: COSV58780115; COSMIC: COSV58780115;