16-46614446-G-A

Position:

• chr16-46614446-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024745.5(SHCBP1):​c.596+1500C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 151,938 control chromosomes in the GnomAD database, including 10,506 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 0.33 (10506 hom., cov: 32)
• Consequence: SHCBP1 NM_024745.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800

Genes affected

SHCBP1 (HGNC:29547): (SHC binding and spindle associated 1) Predicted to enable SH2 domain binding activity. Predicted to be involved in fibroblast growth factor receptor signaling pathway and regulation of neural precursor cell proliferation. Predicted to be located in cytoplasm; midbody; and spindle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHCBP1	NM_024745.5	c.596+1500C>T		intron_variant		ENST00000303383.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHCBP1	ENST00000303383.8	c.596+1500C>T		intron_variant		1	NM_024745.5	P1
SHCBP1	ENST00000566016.5	n.605+1500C>T		intron_variant, non_coding_transcript_variant		1
SHCBP1	ENST00000569702.1	c.48+1500C>T		intron_variant		3
SHCBP1	ENST00000565887.1	n.38+1500C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50131 AN: 151818 Hom.: 10508 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.0425

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.330 AC: 50136 AN: 151938 Hom.: 10506 Cov.: 32 AF XY: 0.326 AC XY: 24198 AN XY: 74232

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.346

Gnomad4 ASJ AF: 0.446

Gnomad4 EAS AF: 0.0426

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.402

Gnomad4 NFE AF: 0.471

Gnomad4 OTH AF: 0.368

Alfa AF: 0.410 Hom.: 2379

Bravo AF: 0.313

Asia WGS AF: 0.152 AC: 534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.41
DANN	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs17734120; hg19: chr16-46648358;