rs7075840

Variant names:

• chr10-80603648-A-G
• rs7075840
• NM_001388272.1:c.713A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-80603648-A-G
• chr10-80603648-A-T

Variant summary

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

The NM_001388272.1(SH2D4B):​c.713A>G​(p.His238Arg) variant causes a missense change. The variant allele was found at a frequency of 0.27 in 1,602,382 control chromosomes in the GnomAD database, including 62,381 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H238Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.32 (8445 hom., cov: 33)
  • Exomes 𝑓: 0.26 (53936 hom.)
• Consequence: SH2D4B NM_001388272.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.92
• Publications: 19 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=0.0018744469).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH2D4B	NM_001388272.1	c.713A>G	p.His238Arg	missense_variant	Exon 5 of 8	ENST00000646907.2	NP_001375201.1
SH2D4B	NM_207372.2	c.713A>G	p.His238Arg	missense_variant	Exon 5 of 7		NP_997255.2
SH2D4B	NM_001145719.1	c.566A>G	p.His189Arg	missense_variant	Exon 5 of 7		NP_001139191.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH2D4B	ENST00000646907.2	c.713A>G	p.His238Arg	missense_variant	Exon 5 of 8		NM_001388272.1	ENSP00000494732.1
SH2D4B	ENST00000339284.6	c.713A>G	p.His238Arg	missense_variant	Exon 5 of 7	2		ENSP00000345295.2
SH2D4B	ENST00000313455.5	c.566A>G	p.His189Arg	missense_variant	Exon 5 of 7	2		ENSP00000314242.4

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48666 AN: 151932 Hom.: 8426 Cov.: 33

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.306

GnomAD2 exomes AF: 0.297 AC: 67986 AN: 228966 AF XY: 0.292

Gnomad AFR exome AF: 0.438

Gnomad AMR exome AF: 0.298

Gnomad ASJ exome AF: 0.317

Gnomad EAS exome AF: 0.496

Gnomad FIN exome AF: 0.290

Gnomad NFE exome AF: 0.246

Gnomad OTH exome AF: 0.286

GnomAD4 exome AF: 0.264 AC: 383232 AN: 1450332 Hom.: 53936 Cov.: 36 AF XY: 0.265 AC XY: 190542 AN XY: 720308

African (AFR) AF: 0.451 AC: 15033 AN: 33358

American (AMR) AF: 0.295 AC: 12623 AN: 42800

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 8098 AN: 25828

East Asian (EAS) AF: 0.551 AC: 21568 AN: 39142

South Asian (SAS) AF: 0.290 AC: 24459 AN: 84314

European-Finnish (FIN) AF: 0.288 AC: 15071 AN: 52258

Middle Eastern (MID) AF: 0.289 AC: 1596 AN: 5528

European-Non Finnish (NFE) AF: 0.242 AC: 267735 AN: 1107148

Other (OTH) AF: 0.284 AC: 17049 AN: 59956

GnomAD4 genome AF: 0.321 AC: 48738 AN: 152050 Hom.: 8445 Cov.: 33 AF XY: 0.321 AC XY: 23877 AN XY: 74324

African (AFR) AF: 0.443 AC: 18367 AN: 41466

American (AMR) AF: 0.282 AC: 4316 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1016 AN: 3470

East Asian (EAS) AF: 0.516 AC: 2652 AN: 5136

South Asian (SAS) AF: 0.302 AC: 1455 AN: 4824

European-Finnish (FIN) AF: 0.291 AC: 3080 AN: 10588

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16926 AN: 67966

Other (OTH) AF: 0.311 AC: 656 AN: 2110

Alfa AF: 0.290 Hom.: 4470

Bravo AF: 0.326

TwinsUK AF: 0.246 AC: 912

ALSPAC AF: 0.252 AC: 970

ESP6500AA AF: 0.433 AC: 1903

ESP6500EA AF: 0.257 AC: 2206

ExAC AF: 0.287 AC: 34732

Asia WGS AF: 0.394 AC: 1367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	14
DANN	Benign	0.65
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.11	T;T;T
MetaRNN	Benign	0.0019	T;T;T
MetaSVM	Benign	-0.95	T
PhyloP100		4.9
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	3.9	N;.;N
REVEL	Benign	0.13
Sift	Benign	1.0	T;.;T
Sift4G	Benign	1.0	T;.;T
Polyphen		0.0	B;.;B
Vest4		0.055
MPC		0.18
ClinPred		0.0045	T
GERP RS		6.0
gMVP		0.34
Mutation Taster		=94/6	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: rs7075840; hg19: chr10-82363404; COSMIC: COSV57893065; COSMIC: COSV57893065;