rs2074022

Positions:

• chr11-2302811-A-G
• chr11-2302811-A-T

Variant summary

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

The NM_139022.3(TSPAN32):​c.67-33A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.903 in 1,586,748 control chromosomes in the GnomAD database, including 653,997 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 0.90 (62022 hom., cov: 32)
  • Exomes 𝑓: 0.90 (591975 hom.)
• Consequence: TSPAN32 NM_139022.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.59

Genes affected

TSPAN32 (HGNC:13410): (tetraspanin 32) This gene, which is a member of the tetraspanin superfamily, is one of several tumor-suppressing subtransferable fragments located in the imprinted gene domain of chromosome 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian and breast cancers. This gene is located among several imprinted genes; however, this gene, as well as the tumor-suppressing subchromosomal transferable fragment 4, escapes imprinting. This gene may play a role in malignancies and diseases that involve this region, and it is also involved in hematopoietic cell function. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

C11orf21 (HGNC:13231): (chromosome 11 open reading frame 21) Predicted to be located in cytoplasm. [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 (MetaRNN=1.9928798E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSPAN32	NM_139022.3	c.67-33A>G		intron_variant		ENST00000182290.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSPAN32	ENST00000182290.9	c.67-33A>G		intron_variant		1	NM_139022.3	P2

Frequencies

GnomAD3 genomes AF: 0.897 AC: 136367 AN: 152070 Hom.: 61973 Cov.: 32

Gnomad AFR AF: 0.953

Gnomad AMI AF: 0.929

Gnomad AMR AF: 0.811

Gnomad ASJ AF: 0.879

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.869

Gnomad FIN AF: 0.831

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.931

Gnomad OTH AF: 0.897

GnomAD3 exomes AF: 0.854 AC: 206535 AN: 241866 Hom.: 90515 AF XY: 0.860 AC XY: 112973 AN XY: 131332

Gnomad AFR exome AF: 0.955

Gnomad AMR exome AF: 0.785

Gnomad ASJ exome AF: 0.878

Gnomad EAS exome AF: 0.413

Gnomad SAS exome AF: 0.870

Gnomad FIN exome AF: 0.838

Gnomad NFE exome AF: 0.929

Gnomad OTH exome AF: 0.884

GnomAD4 exome AF: 0.904 AC: 1296923 AN: 1434560 Hom.: 591975 Cov.: 24 AF XY: 0.903 AC XY: 645689 AN XY: 714706

Gnomad4 AFR exome AF: 0.957

Gnomad4 AMR exome AF: 0.791

Gnomad4 ASJ exome AF: 0.880

Gnomad4 EAS exome AF: 0.432

Gnomad4 SAS exome AF: 0.866

Gnomad4 FIN exome AF: 0.839

Gnomad4 NFE exome AF: 0.932

Gnomad4 OTH exome AF: 0.883

GnomAD4 genome AF: 0.897 AC: 136475 AN: 152188 Hom.: 62022 Cov.: 32 AF XY: 0.887 AC XY: 66010 AN XY: 74382

Gnomad4 AFR AF: 0.953

Gnomad4 AMR AF: 0.810

Gnomad4 ASJ AF: 0.879

Gnomad4 EAS AF: 0.423

Gnomad4 SAS AF: 0.869

Gnomad4 FIN AF: 0.831

Gnomad4 NFE AF: 0.931

Gnomad4 OTH AF: 0.896

Alfa AF: 0.924 Hom.: 85815

Bravo AF: 0.898

TwinsUK AF: 0.938 AC: 3479

ALSPAC AF: 0.927 AC: 3572

ESP6500AA AF: 0.958 AC: 4218

ESP6500EA AF: 0.927 AC: 7970

ExAC AF: 0.862 AC: 104364

Asia WGS AF: 0.741 AC: 2580 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.17
DANN	Benign	0.40
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0086	N
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.0000020	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.90	P;P;P
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.0060
Sift	Pathogenic	0.0	D
Vest4		0.019
ClinPred		0.014	T
GERP RS		-5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2074022; hg19: chr11-2324041; COSMIC: COSV51720820; COSMIC: COSV51720820;