NM_015662.3:c.*2T>C

Variant names:

• chr2-27444430-A-G
• rs4803
• NM_015662.3:c.*2T>C

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.*2T>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 0.401 in 1,597,070 control chromosomes in the GnomAD database, including 134,840 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (17909 hom., cov: 31)
  • Exomes 𝑓: 0.39 (116931 hom.)
• Consequence: IFT172 NM_015662.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.328
• Publications: 41 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 2-27444430-A-G is Benign according to our data. Variant chr2-27444430-A-G is described in ClinVar as Benign. ClinVar VariationId is 379412.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

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.*2T>C		3_prime_UTR	Exon 48 of 48	NP_056477.1	Q9UG01-1
	IFT172	NM_001410739.1		c.*2T>C		3_prime_UTR	Exon 48 of 48	NP_001397668.1	A0A6Q8PGJ2
	KRTCAP3	NM_001168364.2		c.*5+369A>G		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.*2T>C		3_prime_UTR	Exon 48 of 48	ENSP00000260570.3	Q9UG01-1
	IFT172	ENST00000509128.5	TSL:1	n.*697T>C		non_coding_transcript_exon	Exon 16 of 16	ENSP00000427255.1	H0YAI8
	IFT172	ENST00000509128.5	TSL:1	n.*697T>C		3_prime_UTR	Exon 16 of 16	ENSP00000427255.1	H0YAI8

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70447 AN: 151706 Hom.: 17865 Cov.: 31

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.406

GnomAD2 exomes AF: 0.415 AC: 102662 AN: 247210 AF XY: 0.405

Gnomad AFR exome AF: 0.672

Gnomad AMR exome AF: 0.562

Gnomad ASJ exome AF: 0.339

Gnomad EAS exome AF: 0.152

Gnomad FIN exome AF: 0.427

Gnomad NFE exome AF: 0.381

Gnomad OTH exome AF: 0.395

GnomAD4 exome AF: 0.394 AC: 569943 AN: 1445246 Hom.: 116931 Cov.: 29 AF XY: 0.393 AC XY: 282650 AN XY: 719750

African (AFR) AF: 0.676 AC: 22395 AN: 33128

American (AMR) AF: 0.556 AC: 24632 AN: 44314

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 8824 AN: 25994

East Asian (EAS) AF: 0.133 AC: 5270 AN: 39604

South Asian (SAS) AF: 0.418 AC: 35629 AN: 85308

European-Finnish (FIN) AF: 0.431 AC: 22932 AN: 53164

Middle Eastern (MID) AF: 0.346 AC: 1971 AN: 5690

European-Non Finnish (NFE) AF: 0.387 AC: 424923 AN: 1098216

Other (OTH) AF: 0.391 AC: 23367 AN: 59828

GnomAD4 genome AF: 0.465 AC: 70554 AN: 151824 Hom.: 17909 Cov.: 31 AF XY: 0.463 AC XY: 34374 AN XY: 74184

African (AFR) AF: 0.667 AC: 27624 AN: 41404

American (AMR) AF: 0.473 AC: 7217 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1159 AN: 3468

East Asian (EAS) AF: 0.154 AC: 798 AN: 5172

South Asian (SAS) AF: 0.425 AC: 2041 AN: 4800

European-Finnish (FIN) AF: 0.430 AC: 4513 AN: 10506

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

European-Non Finnish (NFE) AF: 0.383 AC: 26029 AN: 67924

Other (OTH) AF: 0.409 AC: 863 AN: 2108

Alfa AF: 0.399 Hom.: 23777

Bravo AF: 0.475

Asia WGS AF: 0.358 AC: 1245 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	Retinal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.59
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs4803; hg19: chr2-27667297; COSMIC: COSV104373920; COSMIC: COSV104373920;