16-1510885-A-G

Position:

• chr16-1510885-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014714.4(IFT140):​c.*59T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,509,780 control chromosomes in the GnomAD database, including 61,079 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (10465 hom., cov: 33)
  • Exomes 𝑓: 0.26 (50614 hom.)
• Consequence: IFT140 NM_014714.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.85

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 16-1510885-A-G is Benign according to our data. Variant chr16-1510885-A-G is described in ClinVar as [Benign]. Clinvar id is 317981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFT140	NM_014714.4	c.*59T>C		3_prime_UTR_variant	31/31	ENST00000426508.7	NP_055529.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFT140	ENST00000426508.7	c.*59T>C		3_prime_UTR_variant	31/31	5	NM_014714.4	ENSP00000406012	P1
IFT140	ENST00000361339.9	c.*59T>C		3_prime_UTR_variant	13/13	1		ENSP00000354895
IFT140	ENST00000565298.5	n.4272T>C		non_coding_transcript_exon_variant	19/19	2
IFT140	ENST00000397417.6	c.*2886T>C		3_prime_UTR_variant, NMD_transcript_variant	24/24	5		ENSP00000380562

Frequencies

GnomAD3 genomes AF: 0.342 AC: 52012 AN: 152076 Hom.: 10443 Cov.: 33

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.327

GnomAD4 exome AF: 0.263 AC: 357435 AN: 1357584 Hom.: 50614 Cov.: 22 AF XY: 0.267 AC XY: 180344 AN XY: 675660

Gnomad4 AFR exome AF: 0.580

Gnomad4 AMR exome AF: 0.161

Gnomad4 ASJ exome AF: 0.287

Gnomad4 EAS exome AF: 0.383

Gnomad4 SAS exome AF: 0.389

Gnomad4 FIN exome AF: 0.254

Gnomad4 NFE exome AF: 0.241

Gnomad4 OTH exome AF: 0.296

GnomAD4 genome AF: 0.342 AC: 52083 AN: 152196 Hom.: 10465 Cov.: 33 AF XY: 0.340 AC XY: 25292 AN XY: 74396

Gnomad4 AFR AF: 0.560

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.270

Gnomad4 EAS AF: 0.354

Gnomad4 SAS AF: 0.392

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.334

Alfa AF: 0.264 Hom.: 7194

Bravo AF: 0.344

Asia WGS AF: 0.433 AC: 1504 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -

Saldino-Mainzer syndrome Benign:2

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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

Retinitis pigmentosa 80 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.12
DANN	Benign	0.40

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: rs1053730; hg19: chr16-1560886; COSMIC: COSV51977497; COSMIC: COSV51977497;