1-154471733-T-C

Position:

• chr1-154471733-T-C

Variant summary

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

The ENST00000486773.1(SHE):​c.103-1371A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 151,928 control chromosomes in the GnomAD database, including 41,225 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 0.73 (41225 hom., cov: 30)
• Consequence: SHE ENST00000486773.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.71

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHE	XM_005244891.6	c.1302-1371A>G		intron_variant			XP_005244948.1
SHE	XM_011509163.4	c.*261-1371A>G		intron_variant			XP_011507465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHE	ENST00000486773.1	c.103-1371A>G		intron_variant		3		ENSP00000452008

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110808 AN: 151810 Hom.: 41212 Cov.: 30

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.873

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.822

Gnomad EAS AF: 0.833

Gnomad SAS AF: 0.766

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.793

Gnomad OTH AF: 0.750

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

GnomAD4 genome AF: 0.730 AC: 110857 AN: 151928 Hom.: 41225 Cov.: 30 AF XY: 0.725 AC XY: 53846 AN XY: 74230

Gnomad4 AFR AF: 0.586

Gnomad4 AMR AF: 0.810

Gnomad4 ASJ AF: 0.822

Gnomad4 EAS AF: 0.833

Gnomad4 SAS AF: 0.766

Gnomad4 FIN AF: 0.653

Gnomad4 NFE AF: 0.793

Gnomad4 OTH AF: 0.751

Alfa AF: 0.758 Hom.: 9782

Bravo AF: 0.738

Asia WGS AF: 0.755 AC: 2626 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.073
DANN	Benign	0.55

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7526293; hg19: chr1-154444209;