16-1510881-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_014714.4(IFT140):c.*63A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00749 in 1,477,856 control chromosomes in the GnomAD database, including 80 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0071 (9 hom., cov: 33)
  • Exomes 𝑓: 0.0075 (71 hom.)
• Consequence: IFT140 NM_014714.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.98

Genes affected

IFT140 (HGNC:29077): (intraflagellar transport 140) This gene encodes one of the subunits of the intraflagellar transport (IFT) complex A. Intraflagellar transport is involved in the genesis, resorption and signaling of primary cilia. The primary cilium is a microtubule-based sensory organelle at the surface of most quiescent mammalian cells, that receives signals from its environment, such as the flow of fluid, light or odors, and transduces those signals to the nucleus. Loss of the corresponding protein in mouse results in renal cystic disease. [provided by RefSeq, Jun 2012]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-1510881-T-C is Benign according to our data. Variant chr16-1510881-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 885377.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00708 (1079/152326) while in subpopulation AMR AF= 0.0102 (156/15312). AF 95% confidence interval is 0.00888. There are 9 homozygotes in gnomad4. There are 583 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFT140	NM_014714.4	c.*63A>G		3_prime_UTR_variant	31/31	ENST00000426508.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFT140	ENST00000426508.7	c.*63A>G		3_prime_UTR_variant	31/31	5	NM_014714.4	P1
IFT140	ENST00000361339.9	c.*63A>G		3_prime_UTR_variant	13/13	1
IFT140	ENST00000565298.5	n.4276A>G		non_coding_transcript_exon_variant	19/19	2
IFT140	ENST00000397417.6	c.*2890A>G		3_prime_UTR_variant, NMD_transcript_variant	24/24	5

Frequencies

GnomAD3 genomes AF: 0.00710 AC: 1081 AN: 152208 Hom.: 9 Cov.: 33

Gnomad AFR AF: 0.00118

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0102

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00600

Gnomad FIN AF: 0.0224

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00766

Gnomad OTH AF: 0.00956

GnomAD4 exome AF: 0.00754 AC: 9993 AN: 1325530 Hom.: 71 Cov.: 20 AF XY: 0.00773 AC XY: 5110 AN XY: 660818

Gnomad4 AFR exome AF: 0.000956

Gnomad4 AMR exome AF: 0.00575

Gnomad4 ASJ exome AF: 0.0106

Gnomad4 EAS exome AF: 0.0000271

Gnomad4 SAS exome AF: 0.00985

Gnomad4 FIN exome AF: 0.0221

Gnomad4 NFE exome AF: 0.00707

Gnomad4 OTH exome AF: 0.00832

GnomAD4 genome AF: 0.00708 AC: 1079 AN: 152326 Hom.: 9 Cov.: 33 AF XY: 0.00783 AC XY: 583 AN XY: 74488

Gnomad4 AFR AF: 0.00118

Gnomad4 AMR AF: 0.0102

Gnomad4 ASJ AF: 0.0104

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00579

Gnomad4 FIN AF: 0.0224

Gnomad4 NFE AF: 0.00766

Gnomad4 OTH AF: 0.00899

Alfa AF: 0.00677 Hom.: 1

Bravo AF: 0.00640

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Saldino-Mainzer syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.60
Dann	Benign	0.65

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: rs149678731; hg19: chr16-1560882;