chr15-48954041-A-G

Variant names:

• chr15-48954041-A-G
• rs16961937
• NM_203349.4:c.585+8390T>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.585+8390T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,242 control chromosomes in the GnomAD database, including 1,077 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 0.11 (1077 hom., cov: 32)
• Consequence: SHC4 NM_203349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.156
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.165 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHC4	NM_203349.4	MANE Select	c.585+8390T>C		intron	N/A	NP_976224.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHC4	ENST00000332408.9	TSL:1 MANE Select	c.585+8390T>C		intron	N/A	ENSP00000329668.4

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16609 AN: 152124 Hom.: 1073 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0528

Gnomad FIN AF: 0.0418

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0965

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.109 AC: 16628 AN: 152242 Hom.: 1077 Cov.: 32 AF XY: 0.104 AC XY: 7762 AN XY: 74438

African (AFR) AF: 0.168 AC: 6983 AN: 41534

American (AMR) AF: 0.102 AC: 1553 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 389 AN: 3472

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5190

South Asian (SAS) AF: 0.0529 AC: 255 AN: 4824

European-Finnish (FIN) AF: 0.0418 AC: 444 AN: 10618

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.0965 AC: 6565 AN: 68014

Other (OTH) AF: 0.130 AC: 272 AN: 2100

Alfa AF: 0.101 Hom.: 379

Bravo AF: 0.115

Asia WGS AF: 0.0320 AC: 112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.7
DANN	Benign	0.51
PhyloP100		0.16
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: rs16961937; hg19: chr15-49246238;