17-39917587-G-C

Variant names:

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

Variant summary

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

The NM_001165958.2(GSDMB):​c.-14-257C>G 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 0.18 (213 hom., cov: 0)
  • Exomes 𝑓: 0.12 (214 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.175 AC: 6118 AN: 34888 Hom.: 213 Cov.: 0

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.0231

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.0951

Gnomad EAS AF: 0.00971

Gnomad SAS AF: 0.0888

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.0652

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.187

GnomAD4 exome AF: 0.121 AC: 8164 AN: 67258 Hom.: 214 Cov.: 0 AF XY: 0.118 AC XY: 4151 AN XY: 35172

African (AFR) AF: 0.375 AC: 406 AN: 1084

American (AMR) AF: 0.139 AC: 293 AN: 2110

Ashkenazi Jewish (ASJ) AF: 0.0796 AC: 136 AN: 1708

East Asian (EAS) AF: 0.00311 AC: 3 AN: 966

South Asian (SAS) AF: 0.0932 AC: 736 AN: 7894

European-Finnish (FIN) AF: 0.109 AC: 492 AN: 4524

Middle Eastern (MID) AF: 0.0773 AC: 17 AN: 220

European-Non Finnish (NFE) AF: 0.125 AC: 5647 AN: 45122

Other (OTH) AF: 0.120 AC: 434 AN: 3630

GnomAD4 genome AF: 0.175 AC: 6119 AN: 34912 Hom.: 213 Cov.: 0 AF XY: 0.169 AC XY: 2901 AN XY: 17134

African (AFR) AF: 0.396 AC: 2193 AN: 5532

American (AMR) AF: 0.127 AC: 384 AN: 3024

Ashkenazi Jewish (ASJ) AF: 0.0951 AC: 73 AN: 768

East Asian (EAS) AF: 0.00971 AC: 4 AN: 412

South Asian (SAS) AF: 0.0890 AC: 87 AN: 978

European-Finnish (FIN) AF: 0.116 AC: 430 AN: 3704

Middle Eastern (MID) AF: 0.0682 AC: 3 AN: 44

European-Non Finnish (NFE) AF: 0.146 AC: 2853 AN: 19580

Other (OTH) AF: 0.187 AC: 82 AN: 438

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	-0.91
CADD	Benign	1.3
DANN	Benign	0.43
PhyloP100		-1.3
PromoterAI		-0.00090	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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;