rs12076073

Variant names:

• chr1-154971680-A-G
• rs12076073
• ENST00000368453.8:c.-3-1481T>C

Variant summary

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

The ENST00000368453.8(SHC1):​c.-3-1481T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,230 control chromosomes in the GnomAD database, including 4,674 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 0.16 (4674 hom., cov: 32)
• Consequence: SHC1 ENST00000368453.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149
• Publications: 9 publications found

Genes affected

SHC1 (HGNC:10840): (SHC adaptor protein 1) This gene encodes three main isoforms that differ in activities and subcellular location. While all three are adapter proteins in signal transduction pathways, the longest (p66Shc) may be involved in regulating life span and the effects of reactive oxygen species. The other two isoforms, p52Shc and p46Shc, link activated receptor tyrosine kinases to the Ras pathway by recruitment of the GRB2/SOS complex. p66Shc is not involved in Ras activation. Unlike the other two isoforms, p46Shc is targeted to the mitochondrial matrix. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHC1	XM_047427958.1	c.-1154T>C		5_prime_UTR_variant	Exon 2 of 13		XP_047283914.1
SHC1	XM_047427959.1	c.-1154T>C		5_prime_UTR_variant	Exon 2 of 12		XP_047283915.1
SHC1	NM_003029.5	c.-3-1481T>C		intron_variant	Intron 1 of 12		NP_003020.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHC1	ENST00000368453.8	c.-3-1481T>C		intron_variant	Intron 1 of 12	1		ENSP00000357438.4
SHC1	ENST00000368450.5	c.-3-1481T>C		intron_variant	Intron 1 of 12	1		ENSP00000357435.1
SHC1	ENST00000412170.5	c.-3-1481T>C		intron_variant	Intron 1 of 6	5		ENSP00000398441.1
SHC1	ENST00000366442.2	c.-3-1481T>C		intron_variant	Intron 2 of 5	3		ENSP00000396162.1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23642 AN: 152112 Hom.: 4634 Cov.: 32

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.0560

Gnomad AMR AF: 0.0642

Gnomad ASJ AF: 0.0349

Gnomad EAS AF: 0.00519

Gnomad SAS AF: 0.0509

Gnomad FIN AF: 0.0209

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0367

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.156 AC: 23739 AN: 152230 Hom.: 4674 Cov.: 32 AF XY: 0.151 AC XY: 11275 AN XY: 74444

African (AFR) AF: 0.466 AC: 19326 AN: 41502

American (AMR) AF: 0.0641 AC: 980 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0349 AC: 121 AN: 3470

East Asian (EAS) AF: 0.00520 AC: 27 AN: 5188

South Asian (SAS) AF: 0.0508 AC: 245 AN: 4826

European-Finnish (FIN) AF: 0.0209 AC: 222 AN: 10620

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0367 AC: 2497 AN: 68020

Other (OTH) AF: 0.112 AC: 237 AN: 2108

Alfa AF: 0.0752 Hom.: 4681

Bravo AF: 0.171

Asia WGS AF: 0.0730 AC: 254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.9
DANN	Benign	0.45
PhyloP100		-0.15
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: rs12076073; hg19: chr1-154944156;