16-50188677-A-G

Variant names:

• chr16-50188677-A-G
• rs10521194
• NM_001365324.3:c.639-22646A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001365324.3(TENT4B):​c.639-22646A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0153 in 152,250 control chromosomes in the GnomAD database, including 30 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 0.015 (30 hom., cov: 33)
• Consequence: TENT4B NM_001365324.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.276

Genes affected

TENT4B (HGNC:30758): (terminal nucleotidyltransferase 4B) Enables guanylyltransferase activity and polynucleotide adenylyltransferase activity. Involved in several processes, including RNA metabolic process; negative regulation of telomere maintenance via telomerase; and regulation of mRNA stability. Located in cytoplasm and nucleolus. Part of TRAMP complex. [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=-0.87).
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0153 (2332/152250) while in subpopulation AMR AF= 0.0178 (272/15296). AF 95% confidence interval is 0.0166. There are 30 homozygotes in gnomad4. There are 1189 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2332 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENT4B	NM_001365324.3	c.639-22646A>G		intron_variant	Intron 1 of 11	ENST00000561678.7	NP_001352253.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENT4B	ENST00000561678.7	c.639-22646A>G		intron_variant	Intron 1 of 11	5	NM_001365324.3	ENSP00000455837.3
TENT4B	ENST00000436909.8	c.594-22646A>G		intron_variant	Intron 2 of 12	2		ENSP00000396995.3
TENT4B	ENST00000562717.1	n.100-22646A>G		intron_variant	Intron 1 of 12	5

Frequencies

GnomAD3 genomes AF: 0.0153 AC: 2334 AN: 152132 Hom.: 31 Cov.: 33

Gnomad AFR AF: 0.00263

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0179

Gnomad ASJ AF: 0.0470

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.0472

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0175

Gnomad OTH AF: 0.0282

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

GnomAD4 genome AF: 0.0153 AC: 2332 AN: 152250 Hom.: 30 Cov.: 33 AF XY: 0.0160 AC XY: 1189 AN XY: 74420

Gnomad4 AFR AF: 0.00262

Gnomad4 AMR AF: 0.0178

Gnomad4 ASJ AF: 0.0470

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00290

Gnomad4 FIN AF: 0.0472

Gnomad4 NFE AF: 0.0175

Gnomad4 OTH AF: 0.0279

Alfa AF: 0.0117 Hom.: 7

Bravo AF: 0.0129

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.6
DANN	Benign	0.81

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: rs10521194; hg19: chr16-50222588;