rs2305480

Variant names:

• chr17-39905943-G-A
• rs2305480
• NM_001165958.2:c.931C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-39905943-G-A
• chr17-39905943-G-C
• chr17-39905943-G-T

Variant summary

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

The NM_001165958.2(GSDMB):​c.931C>T​(p.Pro311Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 1,612,900 control chromosomes in the GnomAD database, including 155,927 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict 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 (10857 hom., cov: 31)
  • Exomes 𝑓: 0.44 (145070 hom.)
• Consequence: GSDMB NM_001165958.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.433
• Publications: 217 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 (MetaRNN=1.2097034E-4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.441 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.931C>T	p.Pro311Ser	missense	Exon 9 of 11	NP_001159430.1	Q8TAX9-4
	GSDMB	NM_001388420.1		c.931C>T	p.Pro311Ser	missense	Exon 8 of 10	NP_001375349.1	Q8TAX9-4
	GSDMB	NM_001165959.2		c.904C>T	p.Pro302Ser	missense	Exon 8 of 10	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.931C>T	p.Pro311Ser	missense	Exon 9 of 11	ENSP00000415049.1	Q8TAX9-4
	GSDMB	ENST00000360317.7	TSL:1	c.931C>T	p.Pro311Ser	missense	Exon 8 of 10	ENSP00000353465.3	Q8TAX9-4
	GSDMB	ENST00000394179.5	TSL:1	c.892C>T	p.Pro298Ser	missense	Exon 7 of 9	ENSP00000377733.2	Q8TAX9-3

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53353 AN: 151802 Hom.: 10846 Cov.: 31

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.661

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.356

GnomAD2 exomes AF: 0.396 AC: 99349 AN: 251044 AF XY: 0.404

Gnomad AFR exome AF: 0.136

Gnomad AMR exome AF: 0.324

Gnomad ASJ exome AF: 0.424

Gnomad EAS exome AF: 0.255

Gnomad FIN exome AF: 0.520

Gnomad NFE exome AF: 0.458

Gnomad OTH exome AF: 0.422

GnomAD4 exome AF: 0.440 AC: 642751 AN: 1460978 Hom.: 145070 Cov.: 38 AF XY: 0.439 AC XY: 318713 AN XY: 726816

African (AFR) AF: 0.135 AC: 4513 AN: 33478

American (AMR) AF: 0.330 AC: 14737 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 10977 AN: 26126

East Asian (EAS) AF: 0.264 AC: 10468 AN: 39670

South Asian (SAS) AF: 0.372 AC: 32035 AN: 86216

European-Finnish (FIN) AF: 0.509 AC: 27170 AN: 53396

Middle Eastern (MID) AF: 0.393 AC: 2265 AN: 5766

European-Non Finnish (NFE) AF: 0.464 AC: 515771 AN: 1111252

Other (OTH) AF: 0.411 AC: 24815 AN: 60372

GnomAD4 genome AF: 0.351 AC: 53390 AN: 151922 Hom.: 10857 Cov.: 31 AF XY: 0.355 AC XY: 26343 AN XY: 74246

African (AFR) AF: 0.143 AC: 5944 AN: 41470

American (AMR) AF: 0.374 AC: 5697 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 1431 AN: 3472

East Asian (EAS) AF: 0.269 AC: 1385 AN: 5150

South Asian (SAS) AF: 0.371 AC: 1786 AN: 4814

European-Finnish (FIN) AF: 0.520 AC: 5474 AN: 10532

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

European-Non Finnish (NFE) AF: 0.445 AC: 30225 AN: 67922

Other (OTH) AF: 0.354 AC: 746 AN: 2108

Alfa AF: 0.422 Hom.: 66284

Bravo AF: 0.325

TwinsUK AF: 0.457 AC: 1695

ALSPAC AF: 0.469 AC: 1807

ESP6500AA AF: 0.147 AC: 647

ESP6500EA AF: 0.443 AC: 3808

ExAC AF: 0.390 AC: 47337

Asia WGS AF: 0.365 AC: 1267 AN: 3478

EpiCase AF: 0.451

EpiControl AF: 0.444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	10
DANN	Benign	0.20
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.50	T
MetaRNN	Benign	0.00012	T
MetaSVM	Benign	-0.95	T
PhyloP100		0.43
PrimateAI	Benign	0.28	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.032
Sift	Benign	0.90	T
Sift4G	Benign	0.12	T
Polyphen		0.34	B
Vest4		0.073
MPC		0.21
ClinPred		0.070	T
GERP RS		0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.29
Mutation Taster		=97/3	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: rs2305480; hg19: chr17-38062196; COSMIC: COSV58779652; COSMIC: COSV58779652;