1-154483473-T-C

Position:

• chr1-154483473-T-C

Variant summary

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

The ENST00000304760.3(SHE):​c.*676A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 985,094 control chromosomes in the GnomAD database, including 192,116 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 0.51 (22642 hom., cov: 31)
  • Exomes 𝑓: 0.63 (169474 hom.)
• Consequence: SHE ENST00000304760.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.533

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 = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHE	NM_001010846.3	c.*676A>G		3_prime_UTR_variant	6/6	ENST00000304760.3	NP_001010846.1
SHE	XM_005244891.6	c.1301+2470A>G		intron_variant			XP_005244948.1
SHE	XM_011509163.4	c.*260+416A>G		intron_variant			XP_011507465.1
SHE	NR_135169.2	n.2545A>G		non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHE	ENST00000304760.3	c.*676A>G		3_prime_UTR_variant	6/6	1	NM_001010846.3	ENSP00000307369	P1
SHE	ENST00000555188.5	c.*2466A>G		3_prime_UTR_variant	3/3	1		ENSP00000451961
SHE	ENST00000486773.1	c.102+2470A>G		intron_variant		3		ENSP00000452008

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77124 AN: 151910 Hom.: 22639 Cov.: 31

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.666

Gnomad AMR AF: 0.674

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.605

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.557

GnomAD4 exome AF: 0.634 AC: 528243 AN: 833066 Hom.: 169474 Cov.: 36 AF XY: 0.634 AC XY: 244023 AN XY: 384706

Gnomad4 AFR exome AF: 0.163

Gnomad4 AMR exome AF: 0.727

Gnomad4 ASJ exome AF: 0.649

Gnomad4 EAS exome AF: 0.749

Gnomad4 SAS exome AF: 0.596

Gnomad4 FIN exome AF: 0.486

Gnomad4 NFE exome AF: 0.644

Gnomad4 OTH exome AF: 0.626

GnomAD4 genome AF: 0.507 AC: 77133 AN: 152028 Hom.: 22642 Cov.: 31 AF XY: 0.507 AC XY: 37692 AN XY: 74316

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.674

Gnomad4 ASJ AF: 0.631

Gnomad4 EAS AF: 0.759

Gnomad4 SAS AF: 0.585

Gnomad4 FIN AF: 0.492

Gnomad4 NFE AF: 0.626

Gnomad4 OTH AF: 0.557

Alfa AF: 0.606 Hom.: 28518

Bravo AF: 0.514

Asia WGS AF: 0.594 AC: 2066 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	0.76
DANN	Benign	0.27

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: rs12568083; hg19: chr1-154455949;