1-162397445-G-T

Variant names:

• chr1-162397445-G-T
• rs164124
• NM_053282.5:c.364-130C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000367929.3(SH2D1B):​c.364-130C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000265 in 755,276 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000026 (0 hom.)
• Consequence: SH2D1B ENST00000367929.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.114
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000367929.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH2D1B	NM_053282.5	MANE Select	c.364-130C>A		intron	N/A	NP_444512.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH2D1B	ENST00000367929.3	TSL:1 MANE Select	c.364-130C>A		intron	N/A	ENSP00000356906.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000265 AC: 2 AN: 755276 Hom.: 0 AF XY: 0.00000505 AC XY: 2 AN XY: 396066

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 18688

American (AMR) AF: 0.00 AC: 0 AN: 30264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19020

East Asian (EAS) AF: 0.00 AC: 0 AN: 34488

South Asian (SAS) AF: 0.00 AC: 0 AN: 62940

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37026

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4268

European-Non Finnish (NFE) AF: 0.00000390 AC: 2 AN: 512314

Other (OTH) AF: 0.00 AC: 0 AN: 36268

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000037155), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.68
DANN	Benign	0.40
PhyloP100		0.11

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: rs164124; hg19: chr1-162367235;