chr15-48914600-A-G

Variant names:

• chr15-48914600-A-G
• rs934740
• NM_203349.4:c.656+10279T>C

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+10279T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 152,086 control chromosomes in the GnomAD database, including 43,033 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 0.72 (43033 hom., cov: 32)
• Consequence: SHC4 NM_203349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.897
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHC4	NM_203349.4	c.656+10279T>C		intron_variant	Intron 2 of 11	ENST00000332408.9	NP_976224.3
SHC4	XM_005254375.4	c.107+10279T>C		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+10279T>C		intron_variant	Intron 2 of 11	1	NM_203349.4	ENSP00000329668.4

Frequencies

GnomAD3 genomes AF: 0.724 AC: 110030 AN: 151968 Hom.: 43023 Cov.: 32

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.924

Gnomad AMR AF: 0.836

Gnomad ASJ AF: 0.852

Gnomad EAS AF: 0.802

Gnomad SAS AF: 0.862

Gnomad FIN AF: 0.887

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.847

Gnomad OTH AF: 0.769

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

GnomAD4 genome AF: 0.724 AC: 110070 AN: 152086 Hom.: 43033 Cov.: 32 AF XY: 0.731 AC XY: 54371 AN XY: 74334

African (AFR) AF: 0.395 AC: 16362 AN: 41438

American (AMR) AF: 0.835 AC: 12760 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.852 AC: 2956 AN: 3470

East Asian (EAS) AF: 0.803 AC: 4154 AN: 5176

South Asian (SAS) AF: 0.863 AC: 4156 AN: 4816

European-Finnish (FIN) AF: 0.887 AC: 9388 AN: 10582

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.847 AC: 57588 AN: 68008

Other (OTH) AF: 0.771 AC: 1631 AN: 2116

Alfa AF: 0.813 Hom.: 75997

Bravo AF: 0.707

Asia WGS AF: 0.768 AC: 2673 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	0.43
DANN	Benign	0.42
PhyloP100		-0.90
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: rs934740; hg19: chr15-49206797;