chr6-84736985-G-A

Variant names:

• chr6-84736985-G-A
• rs114400107
• NM_001080508.3:c.1524C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001080508.3(TBX18):​c.1524C>T​(p.Phe508Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000177 in 1,611,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00018 (0 hom.)
• Consequence: TBX18 NM_001080508.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.111
• Publications: 1 publications found

Genes affected

TBX18 (HGNC:11595): (T-box transcription factor 18) This genes codes for a member of an evolutionarily conserved family of transcription factors that plays a crucial role in embryonic development. The family is characterized by the presence of the DNA-binding T-box domain and is divided into five sub-families based on sequence conservation in this domain. The encoded protein belongs to the vertebrate specific Tbx1 sub-family. The protein acts as a transcriptional repressor by antagonizing transcriptional activators in the T-box family. The protein forms homo- or heterodimers with other transcription factors of the T-box family or other transcription factors. [provided by RefSeq, Nov 2012]

TBX18 Gene-Disease associations (from GenCC):

• congenital anomalies of kidney and urinary tract 2

  Inheritance: AD, Unknown Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 6-84736985-G-A is Benign according to our data. Variant chr6-84736985-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2894708.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.111 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000158 (24/152316) while in subpopulation EAS AF = 0.000965 (5/5184). AF 95% confidence interval is 0.00038. There are 0 homozygotes in GnomAd4. There are 10 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 24 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080508.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBX18	NM_001080508.3	MANE Select	c.1524C>T	p.Phe508Phe	synonymous	Exon 8 of 8	NP_001073977.1	O95935

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBX18	ENST00000369663.10	TSL:1 MANE Select	c.1524C>T	p.Phe508Phe	synonymous	Exon 8 of 8	ENSP00000358677.4	O95935
	TBX18	ENST00000606784.5	TSL:1	c.625+1512C>T		intron	N/A	ENSP00000475873.1	U3KQH2

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000129 AC: 32 AN: 248988 AF XY: 0.000127

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000924

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000978

Gnomad OTH exome AF: 0.000330

GnomAD4 exome AF: 0.000179 AC: 261 AN: 1459542 Hom.: 0 Cov.: 31 AF XY: 0.000179 AC XY: 130 AN XY: 725742

African (AFR) AF: 0.000269 AC: 9 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44590

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25946

East Asian (EAS) AF: 0.000479 AC: 19 AN: 39660

South Asian (SAS) AF: 0.0000349 AC: 3 AN: 85866

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53320

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.000201 AC: 223 AN: 1110624

Other (OTH) AF: 0.000116 AC: 7 AN: 60310

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152316 Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10 AN XY: 74474

African (AFR) AF: 0.0000722 AC: 3 AN: 41576

American (AMR) AF: 0.0000654 AC: 1 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000116 Hom.: 0

Bravo AF: 0.000174

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	4.5
DANN	Benign	0.46
PhyloP100		0.11

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: rs114400107; hg19: chr6-85446703; COSMIC: COSV63736769; COSMIC: COSV63736769;