7-139134699-C-T

Variant names:

• chr7-139134699-C-T
• rs35197265
• NM_024926.4:c.48C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_024926.4(IFT56):​c.48C>T​(p.His16His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0109 in 1,613,880 control chromosomes in the GnomAD database, including 606 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.031 (172 hom., cov: 31)
  • Exomes 𝑓: 0.0088 (434 hom.)
• Consequence: IFT56 NM_024926.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.832
• Publications: 6 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 7-139134699-C-T is Benign according to our data. Variant chr7-139134699-C-T is described in ClinVar as [Benign]. Clinvar id is 1625676.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.832 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT56	NM_024926.4	c.48C>T	p.His16His	synonymous_variant	Exon 2 of 18	ENST00000464848.5	NP_079202.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT56	ENST00000464848.5	c.48C>T	p.His16His	synonymous_variant	Exon 2 of 18	1	NM_024926.4	ENSP00000419279.1
IFT56	ENST00000478836.6	c.48C>T	p.His16His	synonymous_variant	Exon 2 of 16	2		ENSP00000419178.2

Frequencies

GnomAD3 genomes AF: 0.0307 AC: 4672 AN: 152082 Hom.: 168 Cov.: 31

Gnomad AFR AF: 0.0804

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0743

Gnomad SAS AF: 0.0188

Gnomad FIN AF: 0.0392

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00200

Gnomad OTH AF: 0.0220

GnomAD2 exomes AF: 0.0204 AC: 5116 AN: 251094 AF XY: 0.0186

Gnomad AFR exome AF: 0.0844

Gnomad AMR exome AF: 0.0204

Gnomad ASJ exome AF: 0.000496

Gnomad EAS exome AF: 0.0665

Gnomad FIN exome AF: 0.0399

Gnomad NFE exome AF: 0.00236

Gnomad OTH exome AF: 0.0147

GnomAD4 exome AF: 0.00884 AC: 12915 AN: 1461680 Hom.: 434 Cov.: 30 AF XY: 0.00888 AC XY: 6459 AN XY: 727148

African (AFR) AF: 0.0860 AC: 2878 AN: 33470

American (AMR) AF: 0.0204 AC: 911 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.000497 AC: 13 AN: 26134

East Asian (EAS) AF: 0.0926 AC: 3674 AN: 39682

South Asian (SAS) AF: 0.0178 AC: 1533 AN: 86224

European-Finnish (FIN) AF: 0.0378 AC: 2016 AN: 53332

Middle Eastern (MID) AF: 0.0114 AC: 66 AN: 5768

European-Non Finnish (NFE) AF: 0.000935 AC: 1040 AN: 1111970

Other (OTH) AF: 0.0130 AC: 784 AN: 60390

GnomAD4 genome AF: 0.0309 AC: 4699 AN: 152200 Hom.: 172 Cov.: 31 AF XY: 0.0326 AC XY: 2426 AN XY: 74414

African (AFR) AF: 0.0806 AC: 3346 AN: 41512

American (AMR) AF: 0.0179 AC: 274 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.0747 AC: 387 AN: 5182

South Asian (SAS) AF: 0.0188 AC: 91 AN: 4828

European-Finnish (FIN) AF: 0.0392 AC: 415 AN: 10594

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00200 AC: 136 AN: 68004

Other (OTH) AF: 0.0222 AC: 47 AN: 2114

Alfa AF: 0.0124 Hom.: 52

Bravo AF: 0.0320

Asia WGS AF: 0.0650 AC: 227 AN: 3478

EpiCase AF: 0.000872

EpiControl AF: 0.000830

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 20, 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	-0.81
CADD	Benign	7.0
DANN	Benign	0.32
PhyloP100		-0.83
Mutation Taster		=100/0	polymorphism (auto)

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: rs35197265; hg19: chr7-138819445; COSMIC: COSV58271530;