1-154483473-T-C

Variant names:

• chr1-154483473-T-C
• rs12568083
• NM_001010846.3:c.*676A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001010846.3(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 NM_001010846.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.533
• Publications: 11 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
SHE	NM_001010846.3	c.*676A>G		3_prime_UTR_variant	Exon 6 of 6	ENST00000304760.3	NP_001010846.1
SHE	NR_135169.2	n.2545A>G		non_coding_transcript_exon_variant	Exon 6 of 6
SHE	XM_011509163.4	c.*260+416A>G		intron_variant	Intron 6 of 6		XP_011507465.1
SHE	XM_005244891.6	c.1301+2470A>G		intron_variant	Intron 5 of 5		XP_005244948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHE	ENST00000304760.3	c.*676A>G		3_prime_UTR_variant	Exon 6 of 6	1	NM_001010846.3	ENSP00000307369.2
SHE	ENST00000555188.5	c.*2466A>G		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000451961.1
SHE	ENST00000486773.1	c.101+2470A>G		intron_variant	Intron 1 of 1	3		ENSP00000452008.1

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

African (AFR) AF: 0.163 AC: 2565 AN: 15784

American (AMR) AF: 0.727 AC: 715 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.649 AC: 3341 AN: 5148

East Asian (EAS) AF: 0.749 AC: 2719 AN: 3628

South Asian (SAS) AF: 0.596 AC: 9817 AN: 16460

European-Finnish (FIN) AF: 0.486 AC: 134 AN: 276

Middle Eastern (MID) AF: 0.602 AC: 976 AN: 1620

European-Non Finnish (NFE) AF: 0.644 AC: 490895 AN: 761870

Other (OTH) AF: 0.626 AC: 17081 AN: 27296

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

African (AFR) AF: 0.197 AC: 8167 AN: 41448

American (AMR) AF: 0.674 AC: 10302 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2191 AN: 3470

East Asian (EAS) AF: 0.759 AC: 3931 AN: 5178

South Asian (SAS) AF: 0.585 AC: 2821 AN: 4822

European-Finnish (FIN) AF: 0.492 AC: 5194 AN: 10548

Middle Eastern (MID) AF: 0.620 AC: 181 AN: 292

European-Non Finnish (NFE) AF: 0.626 AC: 42565 AN: 67972

Other (OTH) AF: 0.557 AC: 1174 AN: 2106

Alfa AF: 0.594 Hom.: 36021

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
PhyloP100		-0.53
Mutation Taster		=100/0	polymorphism (auto)

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: rs12568083; hg19: chr1-154455949;