chr17-29615805-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -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

Sel.	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

Sel.	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.: 33

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1417458 Hom.: 0 Cov.: 32 AF XY: 0.00000285 AC XY: 2 AN XY: 701060

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: 0.0000247 AC: 2 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: 0.00 AC: 0 AN: 1090446

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

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.0050	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.1
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.18	N
REVEL	Benign	0.032
Sift	Benign	0.64	T
Sift4G	Benign	0.61	T
Polyphen		0.0	B
Vest4		0.072
MutPred		0.36		Loss of helix (P = 0.0376)
MVP		0.47
MPC		0.32
ClinPred		0.14	T
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

Other links and lift over

dbSNP: rs2034837228; hg19: chr17-27942823;