rs7025303

Variant names:

• chr9-38040098-C-T
• rs7025303
• NM_003028.3:c.718-23967G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

ENSG00000255872 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHB	NM_003028.3	c.718-23967G>A		intron_variant	Intron 1 of 5	ENST00000377707.4	NP_003019.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHB	ENST00000377707.4	c.718-23967G>A		intron_variant	Intron 1 of 5	1	NM_003028.3	ENSP00000366936.3
ENSG00000255872	ENST00000540557.1	n.718-23967G>A		intron_variant	Intron 1 of 11	5		ENSP00000457548.1

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

African (AFR) AF: 0.246 AC: 10204 AN: 41534

American (AMR) AF: 0.452 AC: 6913 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 1978 AN: 3472

East Asian (EAS) AF: 0.139 AC: 718 AN: 5176

South Asian (SAS) AF: 0.539 AC: 2604 AN: 4830

European-Finnish (FIN) AF: 0.503 AC: 5323 AN: 10586

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.579 AC: 39364 AN: 67982

Other (OTH) AF: 0.473 AC: 1000 AN: 2114

Alfa AF: 0.544 Hom.: 39378

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
PhyloP100		-3.5
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: rs7025303; hg19: chr9-38040095;