NM_203349.4:c.656+1767G>A

Variant names:

• chr15-48923112-C-T
• rs1007662
• NM_203349.4:c.656+1767G>A

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+1767G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,056 control chromosomes in the GnomAD database, including 5,977 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 0.28 (5977 hom., cov: 31)
• Consequence: SHC4 NM_203349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0280
• Publications: 9 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHC4	NM_203349.4	c.656+1767G>A		intron_variant	Intron 2 of 11	ENST00000332408.9	NP_976224.3
SHC4	XM_005254375.4	c.107+1767G>A		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+1767G>A		intron_variant	Intron 2 of 11	1	NM_203349.4	ENSP00000329668.4

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42195 AN: 151938 Hom.: 5969 Cov.: 31

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.278 AC: 42235 AN: 152056 Hom.: 5977 Cov.: 31 AF XY: 0.282 AC XY: 20979 AN XY: 74326

African (AFR) AF: 0.282 AC: 11688 AN: 41456

American (AMR) AF: 0.246 AC: 3754 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 636 AN: 3470

East Asian (EAS) AF: 0.283 AC: 1464 AN: 5172

South Asian (SAS) AF: 0.231 AC: 1109 AN: 4810

European-Finnish (FIN) AF: 0.394 AC: 4161 AN: 10558

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.273 AC: 18595 AN: 67996

Other (OTH) AF: 0.250 AC: 528 AN: 2114

Alfa AF: 0.260 Hom.: 9169

Bravo AF: 0.267

Asia WGS AF: 0.248 AC: 866 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.35
DANN	Benign	0.35
PhyloP100		0.028
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: rs1007662; hg19: chr15-49215309;