chr21-36245332-T-G

Variant names:

• chr21-36245332-T-G
• rs4817788
• NM_001320714.2:c.3352T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001320714.2(DOP1B):​c.3352T>G​(p.Cys1118Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.883 in 1,614,036 control chromosomes in the GnomAD database, including 630,928 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.91 (63348 hom., cov: 33)
  • Exomes 𝑓: 0.88 (567580 hom.)
• Consequence: DOP1B NM_001320714.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.69
• Publications: 33 publications found

Genes affected

DOP1B (HGNC:1291): (DOP1 leucine zipper like protein B) Involved in cognition. Located in early endosome membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.577192E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOP1B	NM_001320714.2	c.3352T>G	p.Cys1118Gly	missense_variant	Exon 19 of 37	ENST00000691173.1	NP_001307643.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOP1B	ENST00000691173.1	c.3352T>G	p.Cys1118Gly	missense_variant	Exon 19 of 37		NM_001320714.2	ENSP00000509598.1

Frequencies

GnomAD3 genomes AF: 0.911 AC: 138544 AN: 152142 Hom.: 63291 Cov.: 33

Gnomad AFR AF: 0.976

Gnomad AMI AF: 0.904

Gnomad AMR AF: 0.902

Gnomad ASJ AF: 0.907

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.967

Gnomad FIN AF: 0.896

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.865

Gnomad OTH AF: 0.909

GnomAD2 exomes AF: 0.907 AC: 227753 AN: 251162 AF XY: 0.907

Gnomad AFR exome AF: 0.978

Gnomad AMR exome AF: 0.932

Gnomad ASJ exome AF: 0.913

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.893

Gnomad NFE exome AF: 0.862

Gnomad OTH exome AF: 0.886

GnomAD4 exome AF: 0.880 AC: 1286950 AN: 1461776 Hom.: 567580 Cov.: 120 AF XY: 0.882 AC XY: 641659 AN XY: 727196

African (AFR) AF: 0.981 AC: 32834 AN: 33480

American (AMR) AF: 0.932 AC: 41674 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.911 AC: 23803 AN: 26136

East Asian (EAS) AF: 1.00 AC: 39694 AN: 39700

South Asian (SAS) AF: 0.960 AC: 82793 AN: 86258

European-Finnish (FIN) AF: 0.887 AC: 47283 AN: 53304

Middle Eastern (MID) AF: 0.898 AC: 5182 AN: 5768

European-Non Finnish (NFE) AF: 0.863 AC: 959980 AN: 1112010

Other (OTH) AF: 0.889 AC: 53707 AN: 60396

GnomAD4 genome AF: 0.911 AC: 138660 AN: 152260 Hom.: 63348 Cov.: 33 AF XY: 0.912 AC XY: 67887 AN XY: 74426

African (AFR) AF: 0.976 AC: 40568 AN: 41568

American (AMR) AF: 0.902 AC: 13795 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.907 AC: 3149 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5166 AN: 5170

South Asian (SAS) AF: 0.967 AC: 4663 AN: 4824

European-Finnish (FIN) AF: 0.896 AC: 9493 AN: 10598

Middle Eastern (MID) AF: 0.908 AC: 267 AN: 294

European-Non Finnish (NFE) AF: 0.865 AC: 58813 AN: 68022

Other (OTH) AF: 0.910 AC: 1925 AN: 2116

Alfa AF: 0.882 Hom.: 190872

Bravo AF: 0.913

TwinsUK AF: 0.859 AC: 3187

ALSPAC AF: 0.864 AC: 3328

ESP6500AA AF: 0.973 AC: 4289

ESP6500EA AF: 0.863 AC: 7423

ExAC AF: 0.906 AC: 109951

Asia WGS AF: 0.980 AC: 3405 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.041
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.1
DANN	Benign	0.25
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.083	T
MetaRNN	Benign	5.6e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.8	N
PhyloP100		2.7
PrimateAI	Benign	0.30	T
PROVEAN	Benign	3.9	N
REVEL	Benign	0.040
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.047
MPC		0.22
ClinPred		0.0049	T
GERP RS		2.5
Varity_R		0.028
gMVP		0.32
Mutation Taster		=100/0	polymorphism (auto)

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: rs4817788; hg19: chr21-37617630; COSMIC: COSV67694895; COSMIC: COSV67694895;