Genetic Variant NM_032854.4:c.1346G>A (chr17-29615805-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_032854.4(CORO6):c.1346G>A(p.Arg449Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,417,458 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CORO6
NM_032854.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.11

Publications

0 publications found

Variant links:

Genes affected

CORO6 (HGNC:21356): (coronin 6) Predicted to enable actin filament binding activity. Predicted to be involved in actin filament organization and cell migration. [provided by Alliance of Genome Resources, Apr 2022]

CORO6 links:

ABHD15-AS1 (HGNC:49685): (ABHD15 antisense RNA 1)

ABHD15-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05169627).

BP6

Variant 17-29615805-C-T is Benign according to our data. Variant chr17-29615805-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2539459.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032854.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CORO6	NM_032854.4	MANE Select	c.1346G>A	p.Arg449Gln	missense	Exon 11 of 11	NP_116243.2	Q6QEF8-5
CORO6	NM_001388431.1		c.1346G>A	p.Arg449Gln	missense	Exon 11 of 11	NP_001375360.1	Q6QEF8-5
CORO6	NM_001388433.1		c.1343G>A	p.Arg448Gln	missense	Exon 11 of 11	NP_001375362.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CORO6	ENST00000388767.8	TSL:2 MANE Select	c.1346G>A	p.Arg449Gln	missense	Exon 11 of 11	ENSP00000373419.3	Q6QEF8-5
CORO6	ENST00000480954.6	TSL:1	n.*671G>A		non_coding_transcript_exon	Exon 7 of 7	ENSP00000464621.1	J3QSC1
CORO6	ENST00000480954.6	TSL:1	n.*671G>A		3_prime_UTR	Exon 7 of 7	ENSP00000464621.1	J3QSC1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000141

AC:

AN:

1417458

Hom.:

Cov.:

AF XY:

0.00000285

AC XY:

AN XY:

701060

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32576

American (AMR)

AF:

0.00

AC:

AN:

37992

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25368

East Asian (EAS)

AF:

0.00

AC:

AN:

37406

South Asian (SAS)

AF:

0.0000247

AC:

AN:

80928

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48712

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5368

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1090446

Other (OTH)

AF:

0.00

AC:

AN:

58662

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0050

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.75

M_CAP

Benign

0.022

MetaRNN

Benign

0.052

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PhyloP100

1.1

PrimateAI

Benign

0.26

PROVEAN

Benign

0.18

REVEL

Benign

0.032

Sift

Benign

0.64

Sift4G

Benign

0.61

Polyphen

0.0

Vest4

0.072

MutPred

0.36

Loss of helix (P = 0.0376)

MVP

0.47

MPC

0.32

ClinPred

0.14

GERP RS

0.25

gMVP

0.098

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over