1-117025878-G-A

Variant names:

• chr1-117025878-G-A
• rs12093834
• NM_001256106.3:c.2798G>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001256106.3(CD101):​c.2798G>A​(p.Arg933Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00445 in 1,612,474 control chromosomes in the GnomAD database, including 249 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.023 (125 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (124 hom.)
• Consequence: CD101 NM_001256106.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.87

Genes affected

CD101 (HGNC:5949): (CD101 molecule) Predicted to enable hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amides. Predicted to be involved in cell surface receptor signaling pathway. Predicted to act upstream of or within positive regulation of myeloid leukocyte differentiation. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

CD101-AS1 (HGNC:55665): (CD101 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016238093).
• BP6: Variant 1-117025878-G-A is Benign according to our data. Variant chr1-117025878-G-A is described in ClinVar as [Benign]. Clinvar id is 782386.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD101	NM_001256106.3	c.2798G>A	p.Arg933Gln	missense_variant	Exon 8 of 10	ENST00000682167.1	NP_001243035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD101	ENST00000682167.1	c.2798G>A	p.Arg933Gln	missense_variant	Exon 8 of 10		NM_001256106.3	ENSP00000508039.1
CD101	ENST00000369470.1	c.2798G>A	p.Arg933Gln	missense_variant	Exon 8 of 10	1		ENSP00000358482.1
CD101	ENST00000256652.8	c.2798G>A	p.Arg933Gln	missense_variant	Exon 8 of 9	2		ENSP00000256652.4
CD101-AS1	ENST00000445523.1	n.1418C>T		non_coding_transcript_exon_variant	Exon 4 of 4	2

Frequencies

GnomAD3 genomes AF: 0.0229 AC: 3487 AN: 152132 Hom.: 124 Cov.: 32

Gnomad AFR AF: 0.0799

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00792

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0144

GnomAD3 exomes AF: 0.00629 AC: 1574 AN: 250178 Hom.: 52 AF XY: 0.00451 AC XY: 609 AN XY: 135174

Gnomad AFR exome AF: 0.0847

Gnomad AMR exome AF: 0.00440

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000186

Gnomad OTH exome AF: 0.00262

GnomAD4 exome AF: 0.00252 AC: 3676 AN: 1460224 Hom.: 124 Cov.: 31 AF XY: 0.00225 AC XY: 1632 AN XY: 726152

Gnomad4 AFR exome AF: 0.0850

Gnomad4 AMR exome AF: 0.00490

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000394

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000181

Gnomad4 OTH exome AF: 0.00526

GnomAD4 genome AF: 0.0230 AC: 3500 AN: 152250 Hom.: 125 Cov.: 32 AF XY: 0.0219 AC XY: 1631 AN XY: 74448

Gnomad4 AFR AF: 0.0800

Gnomad4 AMR AF: 0.00785

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.00135 Hom.: 7

Bravo AF: 0.0259

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0758 AC: 334

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.00759 AC: 921

Asia WGS AF: 0.00635 AC: 22 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000297

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.031
DANN	Benign	0.81
DEOGEN2	Benign	0.069	T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0043	N
LIST_S2	Benign	0.63	T;.
MetaRNN	Benign	0.0016	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.46	N;N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.37	N;N
REVEL	Benign	0.048
Sift	Benign	0.50	T;T
Sift4G	Benign	0.40	T;T
Polyphen		0.82	P;P
Vest4		0.080
MVP		0.076
MPC		0.11
ClinPred		0.0054	T
GERP RS		-10
Varity_R		0.017
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs12093834; hg19: chr1-117568500;