16-1510953-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014714.4(IFT140):c.4380C>T(p.Asp1460=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00386 in 1,611,318 control chromosomes in the GnomAD database, including 219 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (117 hom., cov: 33)
  • Exomes 𝑓: 0.0021 (102 hom.)
• Consequence: IFT140 NM_014714.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.21

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 16-1510953-G-A is Benign according to our data. Variant chr16-1510953-G-A is described in ClinVar as [Benign]. Clinvar id is 317985.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.2 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFT140	NM_014714.4	c.4380C>T	p.Asp1460=	synonymous_variant	31/31	ENST00000426508.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFT140	ENST00000426508.7	c.4380C>T	p.Asp1460=	synonymous_variant	31/31	5	NM_014714.4	P1
IFT140	ENST00000361339.9	c.1962C>T	p.Asp654=	synonymous_variant	13/13	1
IFT140	ENST00000565298.5	n.4204C>T		non_coding_transcript_exon_variant	19/19	2
IFT140	ENST00000397417.6	c.*2818C>T		3_prime_UTR_variant, NMD_transcript_variant	24/24	5

Frequencies

GnomAD3 genomes AF: 0.0205 AC: 3123 AN: 152206 Hom.: 116 Cov.: 33

Gnomad AFR AF: 0.0710

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00752

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.0158

GnomAD3 exomes AF: 0.00509 AC: 1252 AN: 245918 Hom.: 42 AF XY: 0.00347 AC XY: 463 AN XY: 133400

Gnomad AFR exome AF: 0.0687

Gnomad AMR exome AF: 0.00403

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000547

Gnomad SAS exome AF: 0.000200

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000171

Gnomad OTH exome AF: 0.00217

GnomAD4 exome AF: 0.00211 AC: 3082 AN: 1458994 Hom.: 102 Cov.: 32 AF XY: 0.00179 AC XY: 1299 AN XY: 725600

Gnomad4 AFR exome AF: 0.0747

Gnomad4 AMR exome AF: 0.00418

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000140

Gnomad4 FIN exome AF: 0.0000189

Gnomad4 NFE exome AF: 0.000112

Gnomad4 OTH exome AF: 0.00412

GnomAD4 genome AF: 0.0205 AC: 3130 AN: 152324 Hom.: 117 Cov.: 33 AF XY: 0.0197 AC XY: 1466 AN XY: 74474

Gnomad4 AFR AF: 0.0710

Gnomad4 AMR AF: 0.00751

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000279

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.00925 Hom.: 27

Bravo AF: 0.0234

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Saldino-Mainzer syndrome Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 06, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.037
Dann	Benign	0.49

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: rs61749517; hg19: chr16-1560954; COSMIC: COSV51979071; COSMIC: COSV51979071;