rs780106

Variant names:

• chr2-27458731-A-C
• rs780106
• NM_015662.3:c.2877+48T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-27458731-A-C
• chr2-27458731-A-G
• chr2-27458731-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015662.3(IFT172):​c.2877+48T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 1,598,526 control chromosomes in the GnomAD database, including 135,281 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (17915 hom., cov: 32)
  • Exomes 𝑓: 0.40 (117366 hom.)
• Consequence: IFT172 NM_015662.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -3.12
• Publications: 23 publications found

Genes affected

IFT172 (HGNC:30391): (intraflagellar transport 172) This gene encodes a subunit of the intraflagellar transport subcomplex IFT-B. Subcomplexes IFT-A and IFT-B are necessary for ciliary assembly and maintenance. Mutations in this gene have been associated with skeletal ciliopathies, with or without polydactyly, such as such short-rib thoracic dysplasias 1, 9 or 10. [provided by RefSeq, Mar 2014]

IFT172 Gene-Disease associations (from GenCC):

• short-rib thoracic dysplasia 10 with or without polydactyly

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• Bardet-Biedl syndrome 20

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa 71

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Bardet-Biedl syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Jeune syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• short-rib thoracic dysplasia 9 with or without polydactyly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 2-27458731-A-C is Benign according to our data. Variant chr2-27458731-A-C is described in ClinVar as Benign. ClinVar VariationId is 1257107.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT172	NM_015662.3	c.2877+48T>G		intron_variant	Intron 26 of 47	ENST00000260570.8	NP_056477.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT172	ENST00000260570.8	c.2877+48T>G		intron_variant	Intron 26 of 47	1	NM_015662.3	ENSP00000260570.3

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70509 AN: 151876 Hom.: 17871 Cov.: 32

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.406

GnomAD2 exomes AF: 0.418 AC: 100972 AN: 241592 AF XY: 0.408

Gnomad AFR exome AF: 0.673

Gnomad AMR exome AF: 0.567

Gnomad ASJ exome AF: 0.340

Gnomad EAS exome AF: 0.154

Gnomad FIN exome AF: 0.430

Gnomad NFE exome AF: 0.384

Gnomad OTH exome AF: 0.399

GnomAD4 exome AF: 0.395 AC: 571988 AN: 1446532 Hom.: 117366 Cov.: 27 AF XY: 0.394 AC XY: 283507 AN XY: 719934

African (AFR) AF: 0.677 AC: 22320 AN: 32976

American (AMR) AF: 0.558 AC: 23896 AN: 42856

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 8651 AN: 25500

East Asian (EAS) AF: 0.134 AC: 5290 AN: 39606

South Asian (SAS) AF: 0.418 AC: 35399 AN: 84640

European-Finnish (FIN) AF: 0.432 AC: 22900 AN: 53000

Middle Eastern (MID) AF: 0.340 AC: 1633 AN: 4806

European-Non Finnish (NFE) AF: 0.388 AC: 428518 AN: 1103390

Other (OTH) AF: 0.391 AC: 23381 AN: 59758

GnomAD4 genome AF: 0.465 AC: 70615 AN: 151994 Hom.: 17915 Cov.: 32 AF XY: 0.463 AC XY: 34415 AN XY: 74300

African (AFR) AF: 0.667 AC: 27641 AN: 41460

American (AMR) AF: 0.474 AC: 7232 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1161 AN: 3470

East Asian (EAS) AF: 0.155 AC: 798 AN: 5162

South Asian (SAS) AF: 0.424 AC: 2046 AN: 4820

European-Finnish (FIN) AF: 0.429 AC: 4531 AN: 10560

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 26031 AN: 67942

Other (OTH) AF: 0.410 AC: 864 AN: 2108

Alfa AF: 0.413 Hom.: 11919

Bravo AF: 0.475

Asia WGS AF: 0.358 AC: 1244 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Short-rib thoracic dysplasia 10 with or without polydactyly Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinitis pigmentosa 71 Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.18
DANN	Benign	0.33
PhyloP100		-3.1
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: rs780106; hg19: chr2-27681598; COSMIC: COSV53132994; COSMIC: COSV53132994;