chr2-27215520-C-T

Variant names:

• chr2-27215520-C-T
• rs147821107
• NM_001170795.4:c.340C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001170795.4(ATRAID):​c.340C>T​(p.Arg114Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000855 in 1,614,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R114H) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000085 (0 hom.)
• Consequence: ATRAID NM_001170795.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.75
• Publications: 2 publications found

Genes affected

ATRAID (HGNC:24090): (all-trans retinoic acid induced differentiation factor) This gene is thought to be involved in apoptosis, and may also be involved in hematopoietic development and differentiation. The use of alternative splice sites and promotors result in multiple transcript variants encoding different isoforms.[provided by RefSeq, Dec 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.33905172).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001170795.4. 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
	ATRAID	NM_001170795.4	MANE Select	c.340C>T	p.Arg114Cys	missense	Exon 4 of 7	NP_001164266.1	Q6UW56-1
	ATRAID	NM_016085.5		c.166C>T	p.Arg56Cys	missense	Exon 4 of 7	NP_057169.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATRAID	ENST00000380171.9	TSL:1 MANE Select	c.340C>T	p.Arg114Cys	missense	Exon 4 of 7	ENSP00000369518.4	Q6UW56-1
	ATRAID	ENST00000405489.7	TSL:1	c.166C>T	p.Arg56Cys	missense	Exon 4 of 7	ENSP00000384033.3	Q6UW56-2
	ATRAID	ENST00000892973.1		c.340C>T	p.Arg114Cys	missense	Exon 4 of 7	ENSP00000563032.1

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152198 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000994 AC: 25 AN: 251472 AF XY: 0.000125

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000149

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.0000848 AC: 124 AN: 1461874 Hom.: 0 Cov.: 32 AF XY: 0.0000908 AC XY: 66 AN XY: 727234

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000894 AC: 4 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000926 AC: 103 AN: 1112010

Other (OTH) AF: 0.000116 AC: 7 AN: 60396

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152198 Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8 AN XY: 74352

African (AFR) AF: 0.00 AC: 0 AN: 41448

American (AMR) AF: 0.000327 AC: 5 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5206

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000174 Hom.: 1

Bravo AF: 0.000102

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.0000741 AC: 9

EpiCase AF: 0.000218

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.15
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.053	T
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		2.8
PrimateAI	Benign	0.19	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.21
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.95	P
Vest4		0.31
MVP		0.56
MPC		0.25
ClinPred		0.29	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.089
gMVP		0.66
Mutation Taster		=79/21	polymorphism

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: rs147821107; hg19: chr2-27438388;