chr2-27444495-G-A

Variant names:

• chr2-27444495-G-A
• rs143671920
• NM_015662.3:c.5187C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS1

The NM_015662.3(IFT172):​c.5187C>T​(p.Asp1729Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00018 in 1,613,624 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00025 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (1 hom.)
• Consequence: IFT172 NM_015662.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.06
• Publications: 1 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]

KRTCAP3 (HGNC:28943): (keratinocyte associated protein 3) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 2-27444495-G-A is Benign according to our data. Variant chr2-27444495-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 707015.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.06 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00025 (38/152258) while in subpopulation SAS AF = 0.00186 (9/4826). AF 95% confidence interval is 0.000972. There are 1 homozygotes in GnomAd4. There are 19 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015662.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT172	NM_015662.3	MANE Select	c.5187C>T	p.Asp1729Asp	synonymous	Exon 48 of 48	NP_056477.1	Q9UG01-1
	IFT172	NM_001410739.1		c.5121C>T	p.Asp1707Asp	synonymous	Exon 48 of 48	NP_001397668.1	A0A6Q8PGJ2
	KRTCAP3	NM_001168364.2		c.*5+434G>A		intron	N/A	NP_001161836.1	Q53RY4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT172	ENST00000260570.8	TSL:1 MANE Select	c.5187C>T	p.Asp1729Asp	synonymous	Exon 48 of 48	ENSP00000260570.3	Q9UG01-1
	IFT172	ENST00000509128.5	TSL:1	n.*632C>T		non_coding_transcript_exon	Exon 16 of 16	ENSP00000427255.1	H0YAI8
	IFT172	ENST00000509128.5	TSL:1	n.*632C>T		3_prime_UTR	Exon 16 of 16	ENSP00000427255.1	H0YAI8

Frequencies

GnomAD3 genomes AF: 0.000256 AC: 39 AN: 152140 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000603

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000319 AC: 80 AN: 250700 AF XY: 0.000406

Gnomad AFR exome AF: 0.000371

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000706

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000173 AC: 253 AN: 1461366 Hom.: 1 Cov.: 31 AF XY: 0.000223 AC XY: 162 AN XY: 726964

African (AFR) AF: 0.000956 AC: 32 AN: 33466

American (AMR) AF: 0.0000447 AC: 2 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00172 AC: 148 AN: 86112

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5756

European-Non Finnish (NFE) AF: 0.0000432 AC: 48 AN: 1111740

Other (OTH) AF: 0.000331 AC: 20 AN: 60376

GnomAD4 genome AF: 0.000250 AC: 38 AN: 152258 Hom.: 1 Cov.: 32 AF XY: 0.000255 AC XY: 19 AN XY: 74454

African (AFR) AF: 0.000602 AC: 25 AN: 41548

American (AMR) AF: 0.0000654 AC: 1 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00186 AC: 9 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000773 Hom.: 0

Bravo AF: 0.000181

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Retinal dystrophy (1)
-	-	1	Short-rib thoracic dysplasia 10 with or without polydactyly;C4225342:Retinitis pigmentosa 71 (1)
-	-	1	Short-rib thoracic dysplasia 10 with or without polydactyly;C4225342:Retinitis pigmentosa 71;C4310707:Bardet-Biedl syndrome 20 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	1.4
DANN	Benign	0.68
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs143671920; hg19: chr2-27667362;