Variant 8-140511510-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017444.6(CHRAC1):c.11T>C(p.Val4Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CHRAC1
NM_017444.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0410

Variant links:

Genes affected

CHRAC1 (HGNC:13544): (chromatin accessibility complex subunit 1) CHRAC1 is a histone-fold protein that interacts with other histone-fold proteins to bind DNA in a sequence-independent manner. These histone-fold protein dimers combine within larger enzymatic complexes for DNA transcription, replication, and packaging.[supplied by OMIM, Apr 2004]

CHRAC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.033998042).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRAC1	NM_017444.6 linkuse as main transcript	c.11T>C	p.Val4Ala	missense_variant	1/3	ENST00000220913.10	NP_059140.1
CHRAC1	NR_023360.3 linkuse as main transcript	n.189T>C		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRAC1	ENST00000220913.10 linkuse as main transcript	c.11T>C	p.Val4Ala	missense_variant	1/3	1	NM_017444.6	ENSP00000220913	P1
CHRAC1	ENST00000519533.1 linkuse as main transcript	c.11T>C	p.Val4Ala	missense_variant	1/2	1		ENSP00000428697

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1191066

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

578428

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 06, 2023

The c.11T>C (p.V4A) alteration is located in exon 1 (coding exon 1) of the CHRAC1 gene. This alteration results from a T to C substitution at nucleotide position 11, causing the valine (V) at amino acid position 4 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.69

CADD

Benign

6.9

DANN

Benign

0.61

DEOGEN2

Benign

0.012

T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.35

T;T

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.034

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.20

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.73

PROVEAN

Benign

0.50

N;N

REVEL

Benign

0.017

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.067

MutPred

0.12

Loss of stability (P = 0.0765);Loss of stability (P = 0.0765);

MVP

0.31

MPC

0.021

ClinPred

0.053

GERP RS

-2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.024

gMVP

0.12

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over