9-37921962-G-C

Variant names:

• chr9-37921962-G-C
• rs776008
• NM_003028.3:c.1347-1958C>G

Variant summary

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

The NM_003028.3(SHB):​c.1347-1958C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 152,176 control chromosomes in the GnomAD database, including 14,052 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 0.43 (14052 hom., cov: 34)
• Consequence: SHB NM_003028.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.675
• Publications: 2 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 (NFE) allele frequency at 95% confidence interval = 0.468 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.1347-1958C>G		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.1347-1958C>G		intron	N/A	ENSP00000366936.3
	ENSG00000255872	ENST00000540557.1	TSL:5	n.*560-22012C>G		intron	N/A	ENSP00000457548.1

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64813 AN: 152056 Hom.: 14045 Cov.: 34

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.0924

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.426 AC: 64846 AN: 152176 Hom.: 14052 Cov.: 34 AF XY: 0.422 AC XY: 31391 AN XY: 74398

African (AFR) AF: 0.404 AC: 16750 AN: 41484

American (AMR) AF: 0.400 AC: 6116 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1658 AN: 3472

East Asian (EAS) AF: 0.0921 AC: 477 AN: 5180

South Asian (SAS) AF: 0.416 AC: 2007 AN: 4830

European-Finnish (FIN) AF: 0.405 AC: 4291 AN: 10592

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.472 AC: 32103 AN: 68012

Other (OTH) AF: 0.404 AC: 855 AN: 2114

Alfa AF: 0.335 Hom.: 887

Bravo AF: 0.424

Asia WGS AF: 0.241 AC: 839 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	0.90
DANN	Benign	0.42
PhyloP100		0.68
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: rs776008; hg19: chr9-37921959;