chr14-44904481-C-T

Variant names:

• chr14-44904481-C-T
• rs76976586
• NM_001017923.2:c.701C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001017923.2(DORIP1):​c.701C>T​(p.Ser234Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00233 in 1,612,046 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (47 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (37 hom.)
• Consequence: DORIP1 NM_001017923.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.57
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0068749487).
• BP6: Variant 14-44904481-C-T is Benign according to our data. Variant chr14-44904481-C-T is described in ClinVar as Benign. ClinVar VariationId is 776833.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0128 (1951/152230) while in subpopulation AFR AF = 0.045 (1872/41556). AF 95% confidence interval is 0.0433. There are 47 homozygotes in GnomAd4. There are 901 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 47 gene

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.701C>T	p.Ser234Phe	missense	Exon 4 of 5	NP_001017923.1
	LOC101927418	NR_110050.1		n.162-5168G>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.701C>T	p.Ser234Phe	missense	Exon 4 of 5	ENSP00000326846.3	Q4W4Y0
	DORIP1	ENST00000866783.1		c.701C>T	p.Ser234Phe	missense	Exon 3 of 4	ENSP00000536842.1
	DORIP1	ENST00000866784.1		c.701C>T	p.Ser234Phe	missense	Exon 5 of 6	ENSP00000536843.1

Frequencies

GnomAD3 genomes AF: 0.0128 AC: 1951 AN: 152112 Hom.: 47 Cov.: 33

Gnomad AFR AF: 0.0452

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00386

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: 0.0000736

Gnomad OTH AF: 0.00670

GnomAD2 exomes AF: 0.00327 AC: 818 AN: 250210 AF XY: 0.00228

Gnomad AFR exome AF: 0.0460

Gnomad AMR exome AF: 0.00170

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000441

Gnomad OTH exome AF: 0.00148

GnomAD4 exome AF: 0.00123 AC: 1802 AN: 1459816 Hom.: 37 Cov.: 32 AF XY: 0.00102 AC XY: 737 AN XY: 726096

African (AFR) AF: 0.0470 AC: 1570 AN: 33400

American (AMR) AF: 0.00184 AC: 82 AN: 44576

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39624

South Asian (SAS) AF: 0.0000350 AC: 3 AN: 85758

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53374

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5758

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1110940

Other (OTH) AF: 0.00219 AC: 132 AN: 60284

GnomAD4 genome AF: 0.0128 AC: 1951 AN: 152230 Hom.: 47 Cov.: 33 AF XY: 0.0121 AC XY: 901 AN XY: 74444

African (AFR) AF: 0.0450 AC: 1872 AN: 41556

American (AMR) AF: 0.00392 AC: 60 AN: 15294

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

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

European-Non Finnish (NFE) AF: 0.0000736 AC: 5 AN: 67964

Other (OTH) AF: 0.00664 AC: 14 AN: 2110

Alfa AF: 0.00460 Hom.: 30

Bravo AF: 0.0142

ESP6500AA AF: 0.0474 AC: 209

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00425 AC: 516

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.71	T
MetaRNN	Benign	0.0069	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L
PhyloP100		3.6
PROVEAN	Pathogenic	-5.7	D
REVEL	Benign	0.11
Sift	Benign	0.045	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.83	P
Vest4		0.75
MVP		0.39
MPC		0.052
ClinPred		0.047	T
GERP RS		5.1
Varity_R		0.52
gMVP		0.59
Mutation Taster		=96/4	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: rs76976586; hg19: chr14-45373684;