NM_139022.3:c.67-33A>G

Variant names:

• chr11-2302811-A-G
• rs2074022
• NM_139022.3:c.67-33A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139022.3. 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
	TSPAN32	NM_139022.3	MANE Select	c.67-33A>G		intron	N/A	NP_620591.3
	C11orf21	NR_138249.2		n.259+71T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN32	ENST00000182290.9	TSL:1 MANE Select	c.67-33A>G		intron	N/A	ENSP00000182290.5
	TSPAN32	ENST00000446063.6	TSL:1	n.67-33A>G		intron	N/A	ENSP00000395018.2
	TSPAN32	ENST00000483227.5	TSL:1	n.70-33A>G		intron	N/A

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

GnomAD2 exomes AF: 0.854 AC: 206535 AN: 241866 AF XY: 0.860

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 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

African (AFR) AF: 0.957 AC: 31478 AN: 32884

American (AMR) AF: 0.791 AC: 34742 AN: 43932

Ashkenazi Jewish (ASJ) AF: 0.880 AC: 22689 AN: 25786

East Asian (EAS) AF: 0.432 AC: 17026 AN: 39368

South Asian (SAS) AF: 0.866 AC: 73854 AN: 85300

European-Finnish (FIN) AF: 0.839 AC: 44088 AN: 52534

Middle Eastern (MID) AF: 0.874 AC: 4992 AN: 5710

European-Non Finnish (NFE) AF: 0.932 AC: 1015587 AN: 1089644

Other (OTH) AF: 0.883 AC: 52467 AN: 59402

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

African (AFR) AF: 0.953 AC: 39597 AN: 41546

American (AMR) AF: 0.810 AC: 12391 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.879 AC: 3053 AN: 3472

East Asian (EAS) AF: 0.423 AC: 2176 AN: 5144

South Asian (SAS) AF: 0.869 AC: 4188 AN: 4820

European-Finnish (FIN) AF: 0.831 AC: 8807 AN: 10604

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.931 AC: 63268 AN: 67988

Other (OTH) AF: 0.896 AC: 1893 AN: 2112

Alfa AF: 0.918 Hom.: 191985

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 v4.9

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
PhyloP100		-2.6
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
PromoterAI		-0.0059	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=161/39	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: rs2074022; hg19: chr11-2324041; COSMIC: COSV51720820; COSMIC: COSV51720820;