rs7915642

Variant names:

• chr10-80618105-T-C
• rs7915642
• NM_001388272.1:c.988+8554T>C

Variant summary

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

The NM_001388272.1(SH2D4B):​c.988+8554T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 152,086 control chromosomes in the GnomAD database, including 22,147 homozygotes. 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 0.52 (22147 hom., cov: 32)
• Consequence: SH2D4B NM_001388272.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22
• Publications: 2 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 (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH2D4B	NM_001388272.1	c.988+8554T>C		intron_variant	Intron 6 of 7	ENST00000646907.2	NP_001375201.1
SH2D4B	NM_207372.2	c.985+8554T>C		intron_variant	Intron 6 of 6		NP_997255.2
SH2D4B	NM_001145719.1	c.841+8554T>C		intron_variant	Intron 6 of 6		NP_001139191.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH2D4B	ENST00000646907.2	c.988+8554T>C		intron_variant	Intron 6 of 7		NM_001388272.1	ENSP00000494732.1
SH2D4B	ENST00000339284.6	c.985+8554T>C		intron_variant	Intron 6 of 6	2		ENSP00000345295.2
SH2D4B	ENST00000313455.5	c.841+8554T>C		intron_variant	Intron 6 of 6	2		ENSP00000314242.4
SH2D4B	ENST00000372150.7	n.330+8554T>C		intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79568 AN: 151968 Hom.: 22104 Cov.: 32

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.526

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.524 AC: 79665 AN: 152086 Hom.: 22147 Cov.: 32 AF XY: 0.524 AC XY: 38960 AN XY: 74370

African (AFR) AF: 0.691 AC: 28667 AN: 41510

American (AMR) AF: 0.588 AC: 8985 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 1742 AN: 3468

East Asian (EAS) AF: 0.735 AC: 3807 AN: 5182

South Asian (SAS) AF: 0.282 AC: 1359 AN: 4820

European-Finnish (FIN) AF: 0.404 AC: 4269 AN: 10554

Middle Eastern (MID) AF: 0.445 AC: 130 AN: 292

European-Non Finnish (NFE) AF: 0.429 AC: 29161 AN: 67954

Other (OTH) AF: 0.526 AC: 1111 AN: 2112

Alfa AF: 0.474 Hom.: 2237

Bravo AF: 0.549

Asia WGS AF: 0.513 AC: 1784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.046
DANN	Benign	0.49
PhyloP100		-2.2
Mutation Taster		=100/0	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: rs7915642; hg19: chr10-82377861;