chr14-44905544-G-T

Variant names:

• chr14-44905544-G-T
• rs61742835
• NM_001017923.2:c.927G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001017923.2(DORIP1):​c.927G>T​(p.Glu309Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00594 in 1,505,316 control chromosomes in the GnomAD database, including 445 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (222 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (223 hom.)
• Consequence: DORIP1 NM_001017923.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.81
• Publications: 5 publications found

Genes affected

DORIP1 (HGNC:19834): (chromosome 14 open reading frame 28)

RRAGAP1-AS1 (HGNC:55445): (RRAGAP1 antisense RNA 1)

LOC101927418 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016608238).
• BP6: Variant 14-44905544-G-T is Benign according to our data. Variant chr14-44905544-G-T is described in ClinVar as Benign. ClinVar VariationId is 789639.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017923.2. 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
	DORIP1	NM_001017923.2	MANE Select	c.927G>T	p.Glu309Asp	missense	Exon 5 of 5	NP_001017923.1
	LOC101927418	NR_110050.1		n.161+6213C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DORIP1	ENST00000325192.8	TSL:1 MANE Select	c.927G>T	p.Glu309Asp	missense	Exon 5 of 5	ENSP00000326846.3	Q4W4Y0
	DORIP1	ENST00000866783.1		c.927G>T	p.Glu309Asp	missense	Exon 4 of 4	ENSP00000536842.1
	DORIP1	ENST00000866784.1		c.927G>T	p.Glu309Asp	missense	Exon 6 of 6	ENSP00000536843.1

Frequencies

GnomAD3 genomes AF: 0.0303 AC: 4607 AN: 151974 Hom.: 220 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00865

Gnomad ASJ AF: 0.00289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0191

GnomAD2 exomes AF: 0.00776 AC: 1816 AN: 233896 AF XY: 0.00597

Gnomad AFR exome AF: 0.106

Gnomad AMR exome AF: 0.00550

Gnomad ASJ exome AF: 0.00279

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000167

Gnomad OTH exome AF: 0.00357

GnomAD4 exome AF: 0.00318 AC: 4308 AN: 1353224 Hom.: 223 Cov.: 30 AF XY: 0.00274 AC XY: 1823 AN XY: 665252

African (AFR) AF: 0.109 AC: 3423 AN: 31482

American (AMR) AF: 0.00655 AC: 266 AN: 40612

Ashkenazi Jewish (ASJ) AF: 0.00200 AC: 47 AN: 23470

East Asian (EAS) AF: 0.00 AC: 0 AN: 37894

South Asian (SAS) AF: 0.0000861 AC: 6 AN: 69656

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49256

Middle Eastern (MID) AF: 0.00431 AC: 23 AN: 5340

European-Non Finnish (NFE) AF: 0.000160 AC: 167 AN: 1040854

Other (OTH) AF: 0.00688 AC: 376 AN: 54660

GnomAD4 genome AF: 0.0304 AC: 4628 AN: 152092 Hom.: 222 Cov.: 32 AF XY: 0.0292 AC XY: 2168 AN XY: 74340

African (AFR) AF: 0.107 AC: 4425 AN: 41506

American (AMR) AF: 0.00864 AC: 132 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00289 AC: 10 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 67908

Other (OTH) AF: 0.0189 AC: 40 AN: 2112

Alfa AF: 0.0110 Hom.: 186

Bravo AF: 0.0339

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0947 AC: 417

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.00959 AC: 1164

Asia WGS AF: 0.00780 AC: 27 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	17
DANN	Benign	0.94
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.066
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.69	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.20	N
PhyloP100		1.8
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.076
Sift	Benign	0.14	T
Sift4G	Benign	0.44	T
Polyphen		0.0010	B
Vest4		0.038
MutPred		0.21		Loss of methylation at K310 (P = 0.0601)
MVP		0.23
MPC		0.23
ClinPred		0.0099	T
GERP RS		3.8
Varity_R		0.11
gMVP		0.13
Mutation Taster		=99/1	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: rs61742835; hg19: chr14-45374747;