chr7-139148190-T-C

Variant names:

• chr7-139148190-T-C
• rs17610533
• NM_024926.4:c.546-16T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_024926.4(IFT56):​c.546-16T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0279 in 1,595,136 control chromosomes in the GnomAD database, including 1,233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.035 (144 hom., cov: 32)
  • Exomes 𝑓: 0.027 (1089 hom.)
• Consequence: IFT56 NM_024926.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.277
• Publications: 5 publications found

Genes affected

IFT56 (HGNC:21882): (intraflagellar transport 56) Predicted to enable intraciliary transport particle B binding activity. Predicted to be involved in cilium organization; protein localization to cilium; and smoothened signaling pathway. Predicted to act upstream of or within manchette assembly. Predicted to be located in cilium. Predicted to be part of intraciliary transport particle B. Predicted to be active in ciliary basal body and ciliary base. [provided by Alliance of Genome Resources, Apr 2022]

IFT56 Gene-Disease associations (from GenCC):

• biliary, renal, neurologic, and skeletal syndrome

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 7-139148190-T-C is Benign according to our data. Variant chr7-139148190-T-C is described in ClinVar as [Benign]. Clinvar id is 1530874.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT56	NM_024926.4	c.546-16T>C		intron_variant	Intron 6 of 17	ENST00000464848.5	NP_079202.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT56	ENST00000464848.5	c.546-16T>C		intron_variant	Intron 6 of 17	1	NM_024926.4	ENSP00000419279.1
IFT56	ENST00000478836.6	c.399+5885T>C		intron_variant	Intron 5 of 15	2		ENSP00000419178.2

Frequencies

GnomAD3 genomes AF: 0.0355 AC: 5406 AN: 152202 Hom.: 145 Cov.: 32

Gnomad AFR AF: 0.0552

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0280

Gnomad ASJ AF: 0.0484

Gnomad EAS AF: 0.0425

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.0207

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0202

Gnomad OTH AF: 0.0435

GnomAD2 exomes AF: 0.0382 AC: 9506 AN: 248852 AF XY: 0.0421

Gnomad AFR exome AF: 0.0551

Gnomad AMR exome AF: 0.0138

Gnomad ASJ exome AF: 0.0422

Gnomad EAS exome AF: 0.0401

Gnomad FIN exome AF: 0.0205

Gnomad NFE exome AF: 0.0228

Gnomad OTH exome AF: 0.0366

GnomAD4 exome AF: 0.0271 AC: 39095 AN: 1442816 Hom.: 1089 Cov.: 30 AF XY: 0.0298 AC XY: 21324 AN XY: 714942

African (AFR) AF: 0.0561 AC: 1860 AN: 33140

American (AMR) AF: 0.0145 AC: 637 AN: 43984

Ashkenazi Jewish (ASJ) AF: 0.0423 AC: 1087 AN: 25710

East Asian (EAS) AF: 0.0283 AC: 1110 AN: 39290

South Asian (SAS) AF: 0.118 AC: 10107 AN: 85344

European-Finnish (FIN) AF: 0.0211 AC: 1120 AN: 53132

Middle Eastern (MID) AF: 0.0390 AC: 222 AN: 5688

European-Non Finnish (NFE) AF: 0.0191 AC: 20902 AN: 1097068

Other (OTH) AF: 0.0345 AC: 2050 AN: 59460

GnomAD4 genome AF: 0.0355 AC: 5406 AN: 152320 Hom.: 144 Cov.: 32 AF XY: 0.0363 AC XY: 2705 AN XY: 74494

African (AFR) AF: 0.0552 AC: 2296 AN: 41568

American (AMR) AF: 0.0280 AC: 428 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0484 AC: 168 AN: 3470

East Asian (EAS) AF: 0.0426 AC: 221 AN: 5188

South Asian (SAS) AF: 0.124 AC: 600 AN: 4826

European-Finnish (FIN) AF: 0.0207 AC: 220 AN: 10624

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0202 AC: 1376 AN: 68024

Other (OTH) AF: 0.0425 AC: 90 AN: 2116

Alfa AF: 0.0270 Hom.: 93

Bravo AF: 0.0341

Asia WGS AF: 0.0790 AC: 273 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 01, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	12
DANN	Benign	0.79
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs17610533; hg19: chr7-138832936;