rs9306954

Positions:

• chr4-37959085-T-C
• chr4-37959085-T-G

Variant summary

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

The NM_001396959.1(TBC1D1):​c.418-55424T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 152,048 control chromosomes in the GnomAD database, including 30,881 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 0.63 (30881 hom., cov: 32)
• Consequence: TBC1D1 NM_001396959.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.903

Genes affected

TBC1D1 (HGNC:11578): (TBC1 domain family member 1) TBC1D1 is the founding member of a family of proteins sharing a 180- to 200-amino acid TBC domain presumed to have a role in regulating cell growth and differentiation. These proteins share significant homology with TRE2 (USP6; MIM 604334), yeast Bub2, and CDC16 (MIM 603461) (White et al., 2000 [PubMed 10965142]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D1	NM_001396959.1	c.418-55424T>C		intron_variant		ENST00000698857.1	NP_001383888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D1	ENST00000698857.1	c.418-55424T>C		intron_variant			NM_001396959.1	ENSP00000513987	A2
TBC1D1	ENST00000261439.9	c.418-55424T>C		intron_variant		1		ENSP00000261439	P2
TBC1D1	ENST00000508802.5	c.418-55424T>C		intron_variant		2		ENSP00000423651
TBC1D1	ENST00000698858.1	n.466+48725T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95423 AN: 151930 Hom.: 30815 Cov.: 32

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.957

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.623

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

GnomAD4 genome AF: 0.628 AC: 95550 AN: 152048 Hom.: 30881 Cov.: 32 AF XY: 0.635 AC XY: 47186 AN XY: 74324

Gnomad4 AFR AF: 0.702

Gnomad4 AMR AF: 0.693

Gnomad4 ASJ AF: 0.615

Gnomad4 EAS AF: 0.957

Gnomad4 SAS AF: 0.675

Gnomad4 FIN AF: 0.589

Gnomad4 NFE AF: 0.551

Gnomad4 OTH AF: 0.627

Alfa AF: 0.575 Hom.: 10551

Bravo AF: 0.641

Asia WGS AF: 0.822 AC: 2855 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.6
DANN	Benign	0.78

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: rs9306954; hg19: chr4-37960706;