rs6586111

Positions:

• chr10-80617834-T-C
• chr10-80617834-T-G

Variant summary

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

The NM_001388272.1(SH2D4B):​c.988+8283T>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 152,062 control chromosomes in the GnomAD database, including 22,135 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 (22135 hom., cov: 32)
• Consequence: SH2D4B NM_001388272.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149

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 (BayesDel_noAF=-0.86).
• 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/exons	MANE	Protein	UniProt
SH2D4B	NM_001388272.1	c.988+8283T>C		intron_variant		ENST00000646907.2	NP_001375201.1
SH2D4B	NM_001145719.1	c.841+8283T>C		intron_variant			NP_001139191.1
SH2D4B	NM_207372.2	c.985+8283T>C		intron_variant			NP_997255.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH2D4B	ENST00000646907.2	c.988+8283T>C		intron_variant			NM_001388272.1	ENSP00000494732	P1
SH2D4B	ENST00000313455.5	c.841+8283T>C		intron_variant		2		ENSP00000314242
SH2D4B	ENST00000339284.6	c.985+8283T>C		intron_variant		2		ENSP00000345295
SH2D4B	ENST00000372150.7	n.330+8283T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79537 AN: 151944 Hom.: 22092 Cov.: 32

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.524 AC: 79633 AN: 152062 Hom.: 22135 Cov.: 32 AF XY: 0.524 AC XY: 38918 AN XY: 74328

Gnomad4 AFR AF: 0.690

Gnomad4 AMR AF: 0.588

Gnomad4 ASJ AF: 0.502

Gnomad4 EAS AF: 0.734

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.404

Gnomad4 NFE AF: 0.429

Gnomad4 OTH AF: 0.524

Alfa AF: 0.464 Hom.: 6090

Bravo AF: 0.549

Asia WGS AF: 0.514 AC: 1788 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.8
DANN	Benign	0.79

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: rs6586111; hg19: chr10-82377590;