rs7025303

chr9-38040098-C-T

Variant summary

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

The NM_003028.3(SHB):c.718-23967G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 152,198 control chromosomes in the GnomAD database, including 17,254 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 0.45 (17254 hom., cov: 34)
• Consequence: SHB NM_003028.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.50

Genes affected

SHB (HGNC:10838): (SH2 domain containing adaptor protein B) Enables phosphotyrosine residue binding activity. Predicted to be involved in several processes, including angiogenesis; apoptotic process; and signal transduction. Predicted to act upstream of or within several processes, including hematopoietic stem cell proliferation; negative regulation of oocyte maturation; and positive regulation of immune response. Located in cytoplasmic ribonucleoprotein granule; cytosol; and nucleoplasm. [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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHB	NM_003028.3	c.718-23967G>A		intron_variant		ENST00000377707.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHB	ENST00000377707.4	c.718-23967G>A		intron_variant		1	NM_003028.3	P1

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68843 AN: 152080 Hom.: 17251 Cov.: 34

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.476

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

GnomAD4 genome AF: 0.453 AC: 68870 AN: 152198 Hom.: 17254 Cov.: 34 AF XY: 0.450 AC XY: 33446 AN XY: 74388

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.452

Gnomad4 ASJ AF: 0.570

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.539

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.579

Gnomad4 OTH AF: 0.473

Alfa AF: 0.556 Hom.: 32271

Bravo AF: 0.441

Asia WGS AF: 0.337 AC: 1174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.12
Dann	Benign	0.46

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: rs7025303; hg19: chr9-38040095;