chr9-38019804-C-A

Position:

• chr9-38019804-C-A

Variant summary

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

The NM_003028.3(SHB):​c.718-3673G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,034 control chromosomes in the GnomAD database, including 6,539 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 0.29 (6539 hom., cov: 33)
• Consequence: SHB NM_003028.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.360

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHB	NM_003028.3	c.718-3673G>T		intron_variant		ENST00000377707.4	NP_003019.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHB	ENST00000377707.4	c.718-3673G>T		intron_variant		1	NM_003028.3	ENSP00000366936	P1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43918 AN: 151916 Hom.: 6532 Cov.: 33

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.289 AC: 43959 AN: 152034 Hom.: 6539 Cov.: 33 AF XY: 0.287 AC XY: 21343 AN XY: 74346

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.431

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.255

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.297

Gnomad4 OTH AF: 0.287

Alfa AF: 0.213 Hom.: 564

Bravo AF: 0.297

Asia WGS AF: 0.160 AC: 558 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.69
DANN	Benign	0.56

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: rs1320464; hg19: chr9-38019801;