9-38058427-C-T

Variant names:

• chr9-38058427-C-T
• rs4878743
• NM_003028.3:c.717+9502G>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.717+9502G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 152,054 control chromosomes in the GnomAD database, including 36,192 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 0.69 (36192 hom., cov: 32)
• Consequence: SHB NM_003028.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.936
• Publications: 4 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003028.3. 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
	SHB	NM_003028.3	MANE Select	c.717+9502G>A		intron	N/A	NP_003019.2	Q15464-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHB	ENST00000377707.4	TSL:1 MANE Select	c.717+9502G>A		intron	N/A	ENSP00000366936.3	Q15464-1
	ENSG00000255872	ENST00000540557.1	TSL:5	n.717+9502G>A		intron	N/A	ENSP00000457548.1
	SHB	ENST00000920838.1		c.717+9502G>A		intron	N/A	ENSP00000590897.1

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104526 AN: 151936 Hom.: 36135 Cov.: 32

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.849

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.784

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.719

Gnomad OTH AF: 0.689

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

GnomAD4 genome AF: 0.688 AC: 104645 AN: 152054 Hom.: 36192 Cov.: 32 AF XY: 0.686 AC XY: 50963 AN XY: 74316

African (AFR) AF: 0.665 AC: 27586 AN: 41480

American (AMR) AF: 0.662 AC: 10116 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.719 AC: 2493 AN: 3468

East Asian (EAS) AF: 0.460 AC: 2383 AN: 5182

South Asian (SAS) AF: 0.784 AC: 3769 AN: 4808

European-Finnish (FIN) AF: 0.663 AC: 7016 AN: 10576

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.719 AC: 48837 AN: 67940

Other (OTH) AF: 0.691 AC: 1460 AN: 2112

Alfa AF: 0.713 Hom.: 64795

Bravo AF: 0.687

Asia WGS AF: 0.641 AC: 2231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.60
DANN	Benign	0.71
PhyloP100		-0.94
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: rs4878743; hg19: chr9-38058424;