chr17-42681816-G-A

Position:

• chr17-42681816-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_016602.3(CCR10):​c.8C>T​(p.Thr3Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000538 in 1,612,700 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (4 hom., cov: 31)
  • Exomes 𝑓: 0.00041 (5 hom.)
• Consequence: CCR10 NM_016602.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.40

Genes affected

CCR10 (HGNC:4474): (C-C motif chemokine receptor 10) Chemokines are a group of small (approximately 8 to 14 kD), mostly basic, structurally related molecules that regulate cell trafficking of various types of leukocytes through interactions with a subset of 7-transmembrane, G protein-coupled receptors. Chemokines also play fundamental roles in the development, homeostasis, and function of the immune system, and they have effects on cells of the central nervous system as well as on endothelial cells involved in angiogenesis or angiostasis. Chemokines are divided into 2 major subfamilies, CXC and CC, based on the arrangement of the first 2 of the 4 conserved cysteine residues; the 2 cysteines are separated by a single amino acid in CXC chemokines and are adjacent in CC chemokines. CCR10 is the receptor for CCL27 (SCYA27; MIM 604833); CCR10-CCL27 interactions are involved in T cell-mediated skin inflammation (Homey et al., 2002 [PubMed 11821900]).[supplied by OMIM, Mar 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0057807565).
• BP6: Variant 17-42681816-G-A is Benign according to our data. Variant chr17-42681816-G-A is described in ClinVar as [Benign]. Clinvar id is 712744.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00179 (273/152172) while in subpopulation AMR AF= 0.0174 (266/15294). AF 95% confidence interval is 0.0157. There are 4 homozygotes in gnomad4. There are 181 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCR10	NM_016602.3	c.8C>T	p.Thr3Met	missense_variant	1/2	ENST00000332438.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCR10	ENST00000332438.4	c.8C>T	p.Thr3Met	missense_variant	1/2	1	NM_016602.3	P1
	ENST00000593139.1	n.515-177G>A		intron_variant, non_coding_transcript_variant		5
CCR10	ENST00000591568.1	c.-642-1199C>T		intron_variant		3
CCR10	ENST00000591765.1	c.-643+505C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.00180 AC: 274 AN: 152054 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0175

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00152 AC: 381 AN: 250460 Hom.: 2 AF XY: 0.00107 AC XY: 145 AN XY: 135642

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.0104

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00278

GnomAD4 exome AF: 0.000407 AC: 594 AN: 1460528 Hom.: 5 Cov.: 30 AF XY: 0.000325 AC XY: 236 AN XY: 726660

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.0121

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: 0.00000720

Gnomad4 OTH exome AF: 0.000746

GnomAD4 genome AF: 0.00179 AC: 273 AN: 152172 Hom.: 4 Cov.: 31 AF XY: 0.00243 AC XY: 181 AN XY: 74402

Gnomad4 AFR AF: 0.0000723

Gnomad4 AMR AF: 0.0174

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000139 Hom.: 0

Bravo AF: 0.00248

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000972 AC: 118

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.58	T
MetaRNN	Benign	0.0058	T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	0.76	N
MutationTaster	Benign	0.93	D;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.19
Sift	Benign	0.23	T
Sift4G	Benign	0.088	T
Polyphen		1.0	D
Vest4		0.43
MVP		0.92
MPC		2.3
ClinPred		0.057	T
GERP RS		5.3
Varity_R		0.083
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

Other links and lift over

dbSNP: rs143090639; hg19: chr17-40833834; COSMIC: COSV52855644; COSMIC: COSV52855644;