rs164124

Positions:

• chr1-162397445-G-A

Variant summary

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

The NM_053282.5(SH2D1B):​c.364-130C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.65 in 905,384 control chromosomes in the GnomAD database, including 195,613 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 0.59 (27648 hom., cov: 31)
  • Exomes 𝑓: 0.66 (167965 hom.)
• Consequence: SH2D1B NM_053282.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.114

Genes affected

SH2D1B (HGNC:30416): (SH2 domain containing 1B) By binding phosphotyrosines through its free SRC (MIM 190090) homology-2 (SH2) domain, EAT2 regulates signal transduction through receptors expressed on the surface of antigen-presenting cells (Morra et al., 2001 [PubMed 11689425]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -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 = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH2D1B	NM_053282.5	c.364-130C>T		intron_variant		ENST00000367929.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH2D1B	ENST00000367929.3	c.364-130C>T		intron_variant		1	NM_053282.5	P1

Frequencies

GnomAD3 genomes AF: 0.586 AC: 88929 AN: 151804 Hom.: 27635 Cov.: 31

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.657

Gnomad AMR AF: 0.697

Gnomad ASJ AF: 0.696

Gnomad EAS AF: 0.749

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.626

GnomAD4 exome AF: 0.664 AC: 499927 AN: 753462 Hom.: 167965 AF XY: 0.665 AC XY: 262878 AN XY: 395116

Gnomad4 AFR exome AF: 0.353

Gnomad4 AMR exome AF: 0.708

Gnomad4 ASJ exome AF: 0.702

Gnomad4 EAS exome AF: 0.717

Gnomad4 SAS exome AF: 0.665

Gnomad4 FIN exome AF: 0.611

Gnomad4 NFE exome AF: 0.671

Gnomad4 OTH exome AF: 0.657

GnomAD4 genome AF: 0.586 AC: 88976 AN: 151922 Hom.: 27648 Cov.: 31 AF XY: 0.588 AC XY: 43633 AN XY: 74252

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.697

Gnomad4 ASJ AF: 0.696

Gnomad4 EAS AF: 0.748

Gnomad4 SAS AF: 0.660

Gnomad4 FIN AF: 0.595

Gnomad4 NFE AF: 0.675

Gnomad4 OTH AF: 0.623

Alfa AF: 0.665 Hom.: 33064

Bravo AF: 0.581

Asia WGS AF: 0.696 AC: 2420 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	0.78
DANN	Benign	0.30

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: rs164124; hg19: chr1-162367235; COSMIC: COSV63392075;