rs7164451

Variant names:

• chr15-48921859-G-A
• rs7164451
• NM_203349.4:c.656+3020C>T

Variant summary

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

The NM_203349.4(SHC4):​c.656+3020C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 152,058 control chromosomes in the GnomAD database, including 31,365 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 0.64 (31365 hom., cov: 32)
• Consequence: SHC4 NM_203349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.575
• Publications: 4 publications found

Genes affected

SHC4 (HGNC:16743): (SHC adaptor protein 4) Predicted to enable receptor tyrosine kinase binding activity. Predicted to be involved in transmembrane receptor protein tyrosine kinase signaling pathway. Predicted to act upstream of or within several processes, including apoptotic process; positive regulation of cell population proliferation; and stem cell differentiation. Predicted to be located in postsynaptic membrane. Predicted to be active in plasma membrane. [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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHC4	NM_203349.4	c.656+3020C>T		intron_variant	Intron 2 of 11	ENST00000332408.9	NP_976224.3
SHC4	XM_005254375.4	c.107+3020C>T		intron_variant	Intron 2 of 11		XP_005254432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHC4	ENST00000332408.9	c.656+3020C>T		intron_variant	Intron 2 of 11	1	NM_203349.4	ENSP00000329668.4

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97232 AN: 151940 Hom.: 31345 Cov.: 32

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.620

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

GnomAD4 genome AF: 0.640 AC: 97309 AN: 152058 Hom.: 31365 Cov.: 32 AF XY: 0.645 AC XY: 47939 AN XY: 74330

African (AFR) AF: 0.599 AC: 24825 AN: 41450

American (AMR) AF: 0.702 AC: 10725 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1671 AN: 3470

East Asian (EAS) AF: 0.714 AC: 3694 AN: 5174

South Asian (SAS) AF: 0.654 AC: 3153 AN: 4820

European-Finnish (FIN) AF: 0.711 AC: 7517 AN: 10568

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.644 AC: 43789 AN: 67988

Other (OTH) AF: 0.620 AC: 1311 AN: 2114

Alfa AF: 0.634 Hom.: 39841

Bravo AF: 0.637

Asia WGS AF: 0.674 AC: 2344 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.63
DANN	Benign	0.37
PhyloP100		-0.57
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: rs7164451; hg19: chr15-49214056;