4-140637872-G-A

Variant names:

• chr4-140637872-G-A
• rs732611
• NM_015130.3:c.2505+1214C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015130.3(TBC1D9):​c.2505+1214C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,166 control chromosomes in the GnomAD database, including 1,146 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 0.11 (1146 hom., cov: 32)
• Consequence: TBC1D9 NM_015130.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.148
• Publications: 1 publications found

Genes affected

TBC1D9 (HGNC:21710): (TBC1 domain family member 9) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity and intracellular protein transport. [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 (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D9	NM_015130.3	c.2505+1214C>T		intron_variant	Intron 15 of 20	ENST00000442267.3	NP_055945.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D9	ENST00000442267.3	c.2505+1214C>T		intron_variant	Intron 15 of 20	1	NM_015130.3	ENSP00000411197.2

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16268 AN: 152048 Hom.: 1144 Cov.: 32

Gnomad AFR AF: 0.0258

Gnomad AMI AF: 0.0879

Gnomad AMR AF: 0.0757

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.0633

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.107 AC: 16267 AN: 152166 Hom.: 1146 Cov.: 32 AF XY: 0.107 AC XY: 7922 AN XY: 74382

African (AFR) AF: 0.0257 AC: 1069 AN: 41530

American (AMR) AF: 0.0757 AC: 1156 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 493 AN: 3472

East Asian (EAS) AF: 0.0635 AC: 329 AN: 5184

South Asian (SAS) AF: 0.221 AC: 1065 AN: 4824

European-Finnish (FIN) AF: 0.158 AC: 1675 AN: 10578

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10135 AN: 67988

Other (OTH) AF: 0.108 AC: 227 AN: 2106

Alfa AF: 0.136 Hom.: 1574

Bravo AF: 0.0944

Asia WGS AF: 0.125 AC: 437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.2
DANN	Benign	0.77
PhyloP100		0.15
Mutation Taster		=100/0	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: rs732611; hg19: chr4-141559026;