rs11998861

Variant names:

• chr9-37919842-G-A
• rs11998861
• NM_003028.3:c.1509C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-37919842-G-A
• chr9-37919842-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_003028.3(SHB):​c.1509C>T​(p.Pro503Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00171 in 1,613,760 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0085 (20 hom., cov: 31)
  • Exomes 𝑓: 0.0010 (18 hom.)
• Consequence: SHB NM_003028.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.23
• Publications: 1 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 9-37919842-G-A is Benign according to our data. Variant chr9-37919842-G-A is described in ClinVar as Benign. ClinVar VariationId is 714424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.23 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00854 (1300/152274) while in subpopulation AFR AF = 0.0298 (1236/41542). AF 95% confidence interval is 0.0284. There are 20 homozygotes in GnomAd4. There are 588 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 20 gene

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.1509C>T	p.Pro503Pro	synonymous	Exon 6 of 6	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.1509C>T	p.Pro503Pro	synonymous	Exon 6 of 6	ENSP00000366936.3	Q15464-1
	ENSG00000255872	ENST00000540557.1	TSL:5	n.*560-19892C>T		intron	N/A	ENSP00000457548.1
	SHB	ENST00000920838.1		c.1506C>T	p.Pro502Pro	synonymous	Exon 6 of 6	ENSP00000590897.1

Frequencies

GnomAD3 genomes AF: 0.00844 AC: 1284 AN: 152156 Hom.: 18 Cov.: 31

Gnomad AFR AF: 0.0294

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00814

GnomAD2 exomes AF: 0.00234 AC: 583 AN: 249384 AF XY: 0.00189

Gnomad AFR exome AF: 0.0333

Gnomad AMR exome AF: 0.00136

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000133

Gnomad OTH exome AF: 0.000826

GnomAD4 exome AF: 0.00100 AC: 1467 AN: 1461486 Hom.: 18 Cov.: 31 AF XY: 0.000894 AC XY: 650 AN XY: 727046

African (AFR) AF: 0.0335 AC: 1122 AN: 33470

American (AMR) AF: 0.00161 AC: 72 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00127 AC: 7 AN: 5512

European-Non Finnish (NFE) AF: 0.000112 AC: 125 AN: 1111948

Other (OTH) AF: 0.00224 AC: 135 AN: 60352

GnomAD4 genome AF: 0.00854 AC: 1300 AN: 152274 Hom.: 20 Cov.: 31 AF XY: 0.00790 AC XY: 588 AN XY: 74460

African (AFR) AF: 0.0298 AC: 1236 AN: 41542

American (AMR) AF: 0.00242 AC: 37 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68024

Other (OTH) AF: 0.00806 AC: 17 AN: 2110

Alfa AF: 0.00402 Hom.: 4

Bravo AF: 0.0102

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.21
DANN	Benign	0.79
PhyloP100		-4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

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: rs11998861; hg19: chr9-37919839;