rs17107368

chr10-80609463-T-Achr10-80609463-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001388272.1(SH2D4B):c.900T>A(p.Asp300Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,613,990 control chromosomes in the GnomAD database, including 23,937 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 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 0.14 (1990 hom., cov: 31)
  • Exomes 𝑓: 0.17 (21947 hom.)
• Consequence: SH2D4B NM_001388272.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00

Genes affected

SH2D4B (HGNC:31440): (SH2 domain containing 4B) Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003282398).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH2D4B	NM_001388272.1	c.900T>A	p.Asp300Glu	missense_variant	6/8	ENST00000646907.2
SH2D4B	NM_207372.2	c.897T>A	p.Asp299Glu	missense_variant	6/7
SH2D4B	NM_001145719.1	c.753T>A	p.Asp251Glu	missense_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH2D4B	ENST00000646907.2	c.900T>A	p.Asp300Glu	missense_variant	6/8		NM_001388272.1	P1
SH2D4B	ENST00000339284.6	c.897T>A	p.Asp299Glu	missense_variant	6/7	2
SH2D4B	ENST00000313455.5	c.753T>A	p.Asp251Glu	missense_variant	6/7	2
SH2D4B	ENST00000372150.7	n.242T>A		non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21554 AN: 152056 Hom.: 1992 Cov.: 31

Gnomad AFR AF: 0.0476

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.145

GnomAD3 exomes AF: 0.172 AC: 43286 AN: 251404 Hom.: 4276 AF XY: 0.171 AC XY: 23240 AN XY: 135874

Gnomad AFR exome AF: 0.0444

Gnomad AMR exome AF: 0.162

Gnomad ASJ exome AF: 0.175

Gnomad EAS exome AF: 0.369

Gnomad SAS exome AF: 0.118

Gnomad FIN exome AF: 0.200

Gnomad NFE exome AF: 0.170

Gnomad OTH exome AF: 0.176

GnomAD4 exome AF: 0.167 AC: 243889 AN: 1461816 Hom.: 21947 Cov.: 33 AF XY: 0.166 AC XY: 120431 AN XY: 727200

Gnomad4 AFR exome AF: 0.0445

Gnomad4 AMR exome AF: 0.158

Gnomad4 ASJ exome AF: 0.177

Gnomad4 EAS exome AF: 0.398

Gnomad4 SAS exome AF: 0.117

Gnomad4 FIN exome AF: 0.192

Gnomad4 NFE exome AF: 0.165

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.142 AC: 21543 AN: 152174 Hom.: 1990 Cov.: 31 AF XY: 0.145 AC XY: 10798 AN XY: 74378

Gnomad4 AFR AF: 0.0476

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.144

Alfa AF: 0.172 Hom.: 1754

Bravo AF: 0.136

TwinsUK AF: 0.171 AC: 634

ALSPAC AF: 0.153 AC: 589

ESP6500AA AF: 0.0533 AC: 235

ESP6500EA AF: 0.170 AC: 1463

ExAC AF: 0.169 AC: 20519

Asia WGS AF: 0.222 AC: 771 AN: 3478

EpiCase AF: 0.170

EpiControl AF: 0.171

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.87	T
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.7
Dann	Benign	0.74
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0027	N
LIST_S2	Benign	0.66	T;T;T
MetaRNN	Benign	0.0033	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	1.5	N;.;N
REVEL	Benign	0.014
Sift	Benign	1.0	T;.;T
Sift4G	Benign	1.0	T;.;T
Polyphen		0.0010	B;.;B
Vest4		0.023
MPC		0.14
ClinPred		0.00077	T
GERP RS		-6.9
gMVP		0.11

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

Publications

LitVar

Other links and lift over

dbSNP: rs17107368; hg19: chr10-82369219; COSMIC: COSV57892844;