dbSNP rs62131871: KRTCAP3:c.*5+256G>A (chr2-27444317-G-A) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001168364.2(KRTCAP3):c.*5+256G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0613 in 684,038 control chromosomes in the GnomAD database, including 1,897 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.089 ( 897 hom., cov: 32)

Exomes 𝑓: 0.053 ( 1000 hom. )

Consequence

KRTCAP3
NM_001168364.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.27

Variant links:

Genes affected

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

KRTCAP3 links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 2-27444317-G-A is Benign according to our data. Variant chr2-27444317-G-A is described in ClinVar as [Benign]. Clinvar id is 1235989.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT172	NM_015662.3 link	c.*115C>T		downstream_gene_variant		ENST00000260570.8	NP_056477.1	Q9UG01-1
KRTCAP3	NM_173853.4 link	c.*137G>A		downstream_gene_variant		ENST00000288873.7	NP_776252.2	Q53RY4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT172	ENST00000260570.8 link	c.*115C>T		downstream_gene_variant		1	NM_015662.3	ENSP00000260570.3		Q9UG01-1
KRTCAP3	ENST00000288873.7 link	c.*137G>A		downstream_gene_variant		1	NM_173853.4	ENSP00000288873.3		Q53RY4-1

Frequencies

GnomAD3 genomes

AF:

0.0888

AC:

13480

AN:

151804

Hom.:

890

Cov.:

show subpopulations

Gnomad AFR

AF:

0.188

Gnomad AMI

AF:

0.197

Gnomad AMR

AF:

0.0580

Gnomad ASJ

AF:

0.0295

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.0554

Gnomad FIN

AF:

0.0385

Gnomad MID

AF:

0.0637

Gnomad NFE

AF:

0.0542

Gnomad OTH

AF:

0.0852

GnomAD4 exome

AF:

0.0534

AC:

28439

AN:

532116

Hom.:

1000

Cov.:

AF XY:

0.0536

AC XY:

15071

AN XY:

281026

show subpopulations

Gnomad4 AFR exome

AF:

0.192

Gnomad4 AMR exome

AF:

0.0418

Gnomad4 ASJ exome

AF:

0.0295

Gnomad4 EAS exome

AF:

0.000220

Gnomad4 SAS exome

AF:

0.0613

Gnomad4 FIN exome

AF:

0.0383

Gnomad4 NFE exome

AF:

0.0544

Gnomad4 OTH exome

AF:

0.0622

GnomAD4 genome

AF:

0.0889

AC:

13511

AN:

151922

Hom.:

897

Cov.:

AF XY:

0.0850

AC XY:

6313

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.188

Gnomad4 AMR

AF:

0.0579

Gnomad4 ASJ

AF:

0.0295

Gnomad4 EAS

AF:

0.000966

Gnomad4 SAS

AF:

0.0561

Gnomad4 FIN

AF:

0.0385

Gnomad4 NFE

AF:

0.0542

Gnomad4 OTH

AF:

0.0844

Alfa

AF:

0.0741

Hom.:

Bravo

AF:

0.0962

Asia WGS

AF:

0.0310

AC:

107

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 16, 2018

GeneDx

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

-0.88

CADD

Benign

DANN

Benign

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.48

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.48

Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over