15-48851035-G-T

Variant names:

• chr15-48851035-G-T
• rs17467239
• NM_203349.4:c.1303+153C>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.1303+153C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 152,024 control chromosomes in the GnomAD database, including 10,994 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 0.36 (10994 hom., cov: 32)
• Consequence: SHC4 NM_203349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.218
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203349.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHC4	NM_203349.4	MANE Select	c.1303+153C>A		intron	N/A	NP_976224.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHC4	ENST00000332408.9	TSL:1 MANE Select	c.1303+153C>A		intron	N/A	ENSP00000329668.4
	SHC4	ENST00000396535.7	TSL:1	c.574+153C>A		intron	N/A	ENSP00000379786.3
	SHC4	ENST00000537958.5	TSL:2	c.445+153C>A		intron	N/A	ENSP00000443300.1

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54272 AN: 151906 Hom.: 10995 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.419

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

GnomAD4 genome AF: 0.357 AC: 54284 AN: 152024 Hom.: 10994 Cov.: 32 AF XY: 0.353 AC XY: 26246 AN XY: 74294

African (AFR) AF: 0.185 AC: 7668 AN: 41478

American (AMR) AF: 0.399 AC: 6089 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 2035 AN: 3470

East Asian (EAS) AF: 0.345 AC: 1782 AN: 5170

South Asian (SAS) AF: 0.410 AC: 1970 AN: 4808

European-Finnish (FIN) AF: 0.314 AC: 3314 AN: 10560

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.440 AC: 29906 AN: 67958

Other (OTH) AF: 0.416 AC: 877 AN: 2106

Alfa AF: 0.362 Hom.: 2134

Bravo AF: 0.358

Asia WGS AF: 0.300 AC: 1044 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.0
DANN	Benign	0.59
PhyloP100		0.22
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: rs17467239; hg19: chr15-49143232; COSMIC: COSV60118141; COSMIC: COSV60118141;