17-29615805-C-A

Variant names:

• chr17-29615805-C-A
• rs2034837228
• NM_032854.4:c.1346G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032854.4(CORO6):​c.1346G>T​(p.Arg449Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R449Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CORO6 NM_032854.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• Publications: 0 publications found

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]

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.051464587).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CORO6	NM_032854.4	MANE Select	c.1346G>T	p.Arg449Leu	missense	Exon 11 of 11	NP_116243.2	Q6QEF8-5
	CORO6	NM_001388431.1		c.1346G>T	p.Arg449Leu	missense	Exon 11 of 11	NP_001375360.1	Q6QEF8-5
	CORO6	NM_001388433.1		c.1343G>T	p.Arg448Leu	missense	Exon 11 of 11	NP_001375362.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CORO6	ENST00000388767.8	TSL:2 MANE Select	c.1346G>T	p.Arg449Leu	missense	Exon 11 of 11	ENSP00000373419.3	Q6QEF8-5
	CORO6	ENST00000480954.6	TSL:1	n.*671G>T		non_coding_transcript_exon	Exon 7 of 7	ENSP00000464621.1	J3QSC1
	CORO6	ENST00000480954.6	TSL:1	n.*671G>T		3_prime_UTR	Exon 7 of 7	ENSP00000464621.1	J3QSC1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1417458 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 701060

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32576

American (AMR) AF: 0.00 AC: 0 AN: 37992

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25368

East Asian (EAS) AF: 0.00 AC: 0 AN: 37406

South Asian (SAS) AF: 0.00 AC: 0 AN: 80928

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48712

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5368

European-Non Finnish (NFE) AF: 0.00000183 AC: 2 AN: 1090446

Other (OTH) AF: 0.00 AC: 0 AN: 58662

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	10
DANN	Benign	0.92
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.39	N
PhyloP100		1.1
PrimateAI	Benign	0.27	T
PROVEAN	Benign	1.3	N
REVEL	Benign	0.020
Sift	Benign	0.37	T
Sift4G	Benign	0.34	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.39		Loss of ubiquitination at K444 (P = 0.0298)
MVP		0.41
MPC		0.35
ClinPred		0.14	T
GERP RS		0.25
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2034837228; hg19: chr17-27942823;