chr9-37916411-T-C

Variant names:

• chr9-37916411-T-C
• rs3747547
• NM_003028.3:c.*3410A>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.*3410A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,248 control chromosomes in the GnomAD database, including 2,036 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 0.15 (2036 hom., cov: 33)
• Consequence: SHB NM_003028.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.378
• Publications: 13 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHB	NM_003028.3	c.*3410A>G		3_prime_UTR_variant	Exon 6 of 6	ENST00000377707.4	NP_003019.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHB	ENST00000377707.4	c.*3410A>G		3_prime_UTR_variant	Exon 6 of 6	1	NM_003028.3	ENSP00000366936.3
ENSG00000255872	ENST00000540557.1	n.*560-16461A>G		intron_variant	Intron 6 of 11	5		ENSP00000457548.1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22053 AN: 152130 Hom.: 2024 Cov.: 33

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.0956

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.0951

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0962

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.145 AC: 22087 AN: 152248 Hom.: 2036 Cov.: 33 AF XY: 0.144 AC XY: 10691 AN XY: 74448

African (AFR) AF: 0.259 AC: 10766 AN: 41536

American (AMR) AF: 0.120 AC: 1836 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0951 AC: 330 AN: 3470

East Asian (EAS) AF: 0.106 AC: 547 AN: 5176

South Asian (SAS) AF: 0.122 AC: 590 AN: 4832

European-Finnish (FIN) AF: 0.100 AC: 1061 AN: 10610

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0962 AC: 6541 AN: 68008

Other (OTH) AF: 0.139 AC: 293 AN: 2112

Alfa AF: 0.113 Hom.: 2190

Bravo AF: 0.154

Asia WGS AF: 0.126 AC: 441 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	3.9
DANN	Benign	0.70
PhyloP100		-0.38

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: rs3747547; hg19: chr9-37916408;