dbSNP rs10208616: KRTCAP3:c.*61G>A (chr2-27444241-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_173853.4(KRTCAP3):c.*61G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00403 in 645,062 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 39 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 15 hom. )

Consequence

KRTCAP3
NM_173853.4 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.169

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 2-27444241-G-A is Benign according to our data. Variant chr2-27444241-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1211369.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0121 (1845/152244) while in subpopulation AFR AF= 0.0426 (1768/41536). AF 95% confidence interval is 0.0409. There are 39 homozygotes in gnomad4. There are 853 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTCAP3	NM_173853.4 link	c.*61G>A		3_prime_UTR_variant	Exon 7 of 7	ENST00000288873.7	NP_776252.2	Q53RY4-1
IFT172	NM_015662.3 link	c.*191C>T		downstream_gene_variant		ENST00000260570.8	NP_056477.1	Q9UG01-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTCAP3	ENST00000288873.7 link	c.*61G>A		3_prime_UTR_variant	Exon 7 of 7	1	NM_173853.4	ENSP00000288873.3		Q53RY4-1
IFT172	ENST00000260570.8 link	c.*191C>T		downstream_gene_variant		1	NM_015662.3	ENSP00000260570.3		Q9UG01-1

Frequencies

GnomAD3 genomes

AF:

0.0120

AC:

1831

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0423

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00367

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00622

GnomAD4 exome

AF:

0.00153

AC:

756

AN:

492818

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

313

AN XY:

259712

show subpopulations

Gnomad4 AFR exome

AF:

0.0462

Gnomad4 AMR exome

AF:

0.00263

Gnomad4 ASJ exome

AF:

0.000140

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000152

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000778

Gnomad4 OTH exome

AF:

0.00264

GnomAD4 genome

AF:

0.0121

AC:

1845

AN:

152244

Hom.:

Cov.:

AF XY:

0.0115

AC XY:

853

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0426

Gnomad4 AMR

AF:

0.00366

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00268

Hom.:

Bravo

AF:

0.0136

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Oct 31, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

4.3

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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