rs4845632

Variant names:

• chr1-154486456-A-C
• rs4845632
• NM_001010846.3:c.1181+71T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-154486456-A-C
• chr1-154486456-A-G
• chr1-154486456-A-T

Variant summary

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

The NM_001010846.3(SHE):​c.1181+71T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SHE NM_001010846.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126
• Publications: 2 publications found

Genes affected

SHE (HGNC:27004): (Src homology 2 domain containing E) Predicted to enable phosphotyrosine residue binding activity. [provided by Alliance of Genome Resources, Apr 2022]

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=-0.77).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHE	NM_001010846.3	c.1181+71T>G		intron_variant	Intron 4 of 5	ENST00000304760.3	NP_001010846.1
SHE	NR_135169.2	n.1562+71T>G		intron_variant	Intron 4 of 5
SHE	XM_011509163.4	c.1181+71T>G		intron_variant	Intron 4 of 6		XP_011507465.1
SHE	XM_005244891.6	c.1181+71T>G		intron_variant	Intron 4 of 5		XP_005244948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHE	ENST00000304760.3	c.1181+71T>G		intron_variant	Intron 4 of 5	1	NM_001010846.3	ENSP00000307369.2
SHE	ENST00000555188.5	c.272+71T>G		intron_variant	Intron 2 of 2	1		ENSP00000451961.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.07e-7 AC: 1 AN: 1414246 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 699246

⚠️ 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: 31824

American (AMR) AF: 0.0000260 AC: 1 AN: 38408

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23794

East Asian (EAS) AF: 0.00 AC: 0 AN: 39152

South Asian (SAS) AF: 0.00 AC: 0 AN: 80742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51800

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4226

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1086002

Other (OTH) AF: 0.00 AC: 0 AN: 58298

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.4
DANN	Benign	0.78
PhyloP100		-0.13
PromoterAI		-0.014	Neutral

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: rs4845632; hg19: chr1-154458932;