1-154486456-A-G

Variant names:

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

Variant summary

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

The NM_001010846.3(SHE):​c.1181+71T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.985 in 1,566,466 control chromosomes in the GnomAD database, including 762,179 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 0.92 (65357 hom., cov: 32)
  • Exomes 𝑓: 0.99 (696822 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHE	NM_001010846.3	c.1181+71T>C		intron_variant	Intron 4 of 5	ENST00000304760.3	NP_001010846.1
SHE	NR_135169.2	n.1562+71T>C		intron_variant	Intron 4 of 5
SHE	XM_011509163.4	c.1181+71T>C		intron_variant	Intron 4 of 6		XP_011507465.1
SHE	XM_005244891.6	c.1181+71T>C		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>C		intron_variant	Intron 4 of 5	1	NM_001010846.3	ENSP00000307369.2
SHE	ENST00000555188.5	c.272+71T>C		intron_variant	Intron 2 of 2	1		ENSP00000451961.1

Frequencies

GnomAD3 genomes AF: 0.918 AC: 139627 AN: 152136 Hom.: 65326 Cov.: 32

Gnomad AFR AF: 0.712

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.971

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.998

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.953

GnomAD4 exome AF: 0.992 AC: 1402490 AN: 1414212 Hom.: 696822 AF XY: 0.993 AC XY: 694138 AN XY: 699226

African (AFR) AF: 0.705 AC: 22403 AN: 31794

American (AMR) AF: 0.983 AC: 37747 AN: 38408

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 23792 AN: 23794

East Asian (EAS) AF: 1.00 AC: 39151 AN: 39152

South Asian (SAS) AF: 0.999 AC: 80693 AN: 80742

European-Finnish (FIN) AF: 1.00 AC: 51797 AN: 51800

Middle Eastern (MID) AF: 0.986 AC: 4165 AN: 4226

European-Non Finnish (NFE) AF: 1.00 AC: 1085515 AN: 1086000

Other (OTH) AF: 0.982 AC: 57227 AN: 58296

GnomAD4 genome AF: 0.918 AC: 139710 AN: 152254 Hom.: 65357 Cov.: 32 AF XY: 0.920 AC XY: 68498 AN XY: 74446

African (AFR) AF: 0.712 AC: 29543 AN: 41486

American (AMR) AF: 0.971 AC: 14855 AN: 15300

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5188 AN: 5188

South Asian (SAS) AF: 0.999 AC: 4812 AN: 4818

European-Finnish (FIN) AF: 1.00 AC: 10627 AN: 10628

Middle Eastern (MID) AF: 0.983 AC: 289 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67995 AN: 68040

Other (OTH) AF: 0.953 AC: 2017 AN: 2116

Alfa AF: 0.936 Hom.: 10720

Bravo AF: 0.906

Asia WGS AF: 0.985 AC: 3425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.9
DANN	Benign	0.79
PhyloP100		-0.13
PromoterAI		-0.021	Neutral
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: rs4845632; hg19: chr1-154458932;