10-80609463-T-A

Variant names:

• chr10-80609463-T-A
• rs17107368
• NM_001388272.1:c.900T>A

Variant summary

Our verdict is Benign. The variant received -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. 12/18 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
• Publications: 15 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SH2D4B	NM_001388272.1	c.900T>A	p.Asp300Glu	missense_variant	Exon 6 of 8	ENST00000646907.2	NP_001375201.1
SH2D4B	NM_207372.2	c.897T>A	p.Asp299Glu	missense_variant	Exon 6 of 7		NP_997255.2
SH2D4B	NM_001145719.1	c.753T>A	p.Asp251Glu	missense_variant	Exon 6 of 7		NP_001139191.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH2D4B	ENST00000646907.2	c.900T>A	p.Asp300Glu	missense_variant	Exon 6 of 8		NM_001388272.1	ENSP00000494732.1
SH2D4B	ENST00000339284.6	c.897T>A	p.Asp299Glu	missense_variant	Exon 6 of 7	2		ENSP00000345295.2
SH2D4B	ENST00000313455.5	c.753T>A	p.Asp251Glu	missense_variant	Exon 6 of 7	2		ENSP00000314242.4
SH2D4B	ENST00000372150.7	n.242T>A		non_coding_transcript_exon_variant	Exon 2 of 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

GnomAD2 exomes AF: 0.172 AC: 43286 AN: 251404 AF XY: 0.171

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 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

African (AFR) AF: 0.0445 AC: 1491 AN: 33480

American (AMR) AF: 0.158 AC: 7054 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 4613 AN: 26134

East Asian (EAS) AF: 0.398 AC: 15802 AN: 39700

South Asian (SAS) AF: 0.117 AC: 10069 AN: 86254

European-Finnish (FIN) AF: 0.192 AC: 10239 AN: 53418

Middle Eastern (MID) AF: 0.164 AC: 948 AN: 5766

European-Non Finnish (NFE) AF: 0.165 AC: 183562 AN: 1111956

Other (OTH) AF: 0.167 AC: 10111 AN: 60388

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

African (AFR) AF: 0.0476 AC: 1978 AN: 41540

American (AMR) AF: 0.146 AC: 2227 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 625 AN: 3472

East Asian (EAS) AF: 0.384 AC: 1979 AN: 5156

South Asian (SAS) AF: 0.116 AC: 561 AN: 4822

European-Finnish (FIN) AF: 0.205 AC: 2171 AN: 10582

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11460 AN: 67986

Other (OTH) AF: 0.144 AC: 305 AN: 2114

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
PhyloP100		-1.0
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
Mutation Taster		=99/1	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: rs17107368; hg19: chr10-82369219; COSMIC: COSV57892844;