9-38041145-T-G

Variant names:

• chr9-38041145-T-G
• rs7873102
• NM_003028.3:c.718-25014A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003028.3(SHB):​c.718-25014A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 152,008 control chromosomes in the GnomAD database, including 26,471 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 0.59 (26471 hom., cov: 32)
• Consequence: SHB NM_003028.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280
• Publications: 18 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.613 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHB	NM_003028.3	MANE Select	c.718-25014A>C		intron	N/A	NP_003019.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHB	ENST00000377707.4	TSL:1 MANE Select	c.718-25014A>C		intron	N/A	ENSP00000366936.3
	ENSG00000255872	ENST00000540557.1	TSL:5	n.718-25014A>C		intron	N/A	ENSP00000457548.1

Frequencies

GnomAD3 genomes AF: 0.589 AC: 89475 AN: 151890 Hom.: 26436 Cov.: 32

Gnomad AFR AF: 0.619

Gnomad AMI AF: 0.647

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.587

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

GnomAD4 genome AF: 0.589 AC: 89558 AN: 152008 Hom.: 26471 Cov.: 32 AF XY: 0.585 AC XY: 43471 AN XY: 74280

African (AFR) AF: 0.619 AC: 25657 AN: 41456

American (AMR) AF: 0.584 AC: 8922 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 2219 AN: 3466

East Asian (EAS) AF: 0.298 AC: 1539 AN: 5164

South Asian (SAS) AF: 0.611 AC: 2938 AN: 4810

European-Finnish (FIN) AF: 0.530 AC: 5597 AN: 10560

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.599 AC: 40670 AN: 67948

Other (OTH) AF: 0.582 AC: 1231 AN: 2114

Alfa AF: 0.603 Hom.: 31327

Bravo AF: 0.597

Asia WGS AF: 0.433 AC: 1508 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.48
PhyloP100		-0.28
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: rs7873102; hg19: chr9-38041142;