Genetic Variant NM_017750.4:c.1810C>A (chr2-85343265-G-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_017750.4(RETSAT):c.1810C>A(p.Arg604Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00289 in 1,611,840 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 Benign (★★).

Frequency

Genomes: 𝑓 0.0039 ( 0 hom., cov: 36)

Exomes 𝑓: 0.0028 ( 0 hom. )

Consequence

RETSAT
NM_017750.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.36

Publications

3 publications found

Variant links:

Genes affected

RETSAT (HGNC:25991): (retinol saturase) Predicted to enable all-trans-retinol 13,14-reductase activity. Predicted to be involved in retinol metabolic process. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

RETSAT links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

PM2

Variant has high frequency in the EAS (0.0561) population. However there is too low homozygotes in high coverage region: (expected more than 3, got 0).

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 2-85343265-G-T is Benign according to our data. Variant chr2-85343265-G-T is described in ClinVar as Benign. ClinVar VariationId is 771334.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.36 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017750.4. 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
	RETSAT	NM_017750.4	MANE Select	c.1810C>A	p.Arg604Arg	synonymous	Exon 11 of 11	NP_060220.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RETSAT	ENST00000295802.9	TSL:1 MANE Select	c.1810C>A	p.Arg604Arg	synonymous	Exon 11 of 11	ENSP00000295802.4	Q6NUM9-1
RETSAT	ENST00000429806.5	TSL:1	n.*197C>A		non_coding_transcript_exon	Exon 8 of 8	ENSP00000388202.1	H7BZ81
RETSAT	ENST00000429806.5	TSL:1	n.*197C>A		3_prime_UTR	Exon 8 of 8	ENSP00000388202.1	H7BZ81

Frequencies

GnomAD3 genomes

AF:

0.00394

AC:

599

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0139

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.0629

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00808

AC:

2017

AN:

249554

AF XY:

0.00672

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0304

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.0496

Gnomad FIN exome

AF:

0.00213

Gnomad NFE exome

AF:

0.000176

Gnomad OTH exome

AF:

0.00409

GnomAD4 exome

AF:

0.00278

AC:

4064

AN:

1459662

Hom.:

Cov.:

AF XY:

0.00263

AC XY:

1910

AN XY:

726270

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000179

AC:

AN:

33472

American (AMR)

AF:

0.0308

AC:

1359

AN:

44124

Ashkenazi Jewish (ASJ)

AF:

0.00165

AC:

AN:

26122

East Asian (EAS)

AF:

0.0581

AC:

2227

AN:

38338

South Asian (SAS)

AF:

0.00107

AC:

AN:

86220

European-Finnish (FIN)

AF:

0.00118

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000818

AC:

AN:

1111940

Other (OTH)

AF:

0.00302

AC:

182

AN:

60290

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

390

780

1170

1560

1950

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

124

186

248

310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00395

AC:

601

AN:

152178

Hom.:

Cov.:

AF XY:

0.00425

AC XY:

316

AN XY:

74400

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000192

AC:

AN:

41602

American (AMR)

AF:

0.0139

AC:

211

AN:

15232

Ashkenazi Jewish (ASJ)

AF:

0.00432

AC:

AN:

3472

East Asian (EAS)

AF:

0.0636

AC:

322

AN:

5060

South Asian (SAS)

AF:

0.000827

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00188

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68036

Other (OTH)

AF:

0.00331

AC:

AN:

2112

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.282

Heterozygous variant carriers

148

197

246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000261

Hom.:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.5

(source)

DANN

Benign

0.36

PhyloP100

1.4

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over