Genetic Variant NM_014901.5:c.1236+18T>G (chr5-176529270-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014901.5(RNF44):c.1236+18T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.879 in 1,608,772 control chromosomes in the GnomAD database, including 623,582 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.90 ( 62523 hom., cov: 34)

Exomes 𝑓: 0.88 ( 561059 hom. )

Consequence

RNF44
NM_014901.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -7.23

Publications

24 publications found

Variant links:

Genes affected

RNF44 (HGNC:19180): (ring finger protein 44) The protein encoded by this gene contains a RING finger, a motif present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions. [provided by RefSeq, Jul 2008]

RNF44 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (REVEL=0.003).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014901.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF44	NM_014901.5	MANE Select	c.1236+18T>G		intron	N/A	NP_055716.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RNF44	ENST00000274811.9	TSL:1 MANE Select	c.1236+18T>G		intron	N/A	ENSP00000274811.4
RNF44	ENST00000506378.2	TSL:2	c.1254T>G	p.Ser418Ser	synonymous	Exon 10 of 10	ENSP00000425253.2
RNF44	ENST00000939391.1		c.1263+18T>G		intron	N/A	ENSP00000609450.1

Frequencies

GnomAD3 genomes

AF:

0.904

AC:

137602

AN:

152200

Hom.:

62460

Cov.:

show subpopulations

Gnomad AFR

AF:

0.973

Gnomad AMI

AF:

0.925

Gnomad AMR

AF:

0.874

Gnomad ASJ

AF:

0.873

Gnomad EAS

AF:

0.781

Gnomad SAS

AF:

0.707

Gnomad FIN

AF:

0.930

Gnomad MID

AF:

0.845

Gnomad NFE

AF:

0.890

Gnomad OTH

AF:

0.895

GnomAD2 exomes

AF:

0.860

AC:

214793

AN:

249740

AF XY:

0.853

show subpopulations

Gnomad AFR exome

AF:

0.974

Gnomad AMR exome

AF:

0.851

Gnomad ASJ exome

AF:

0.862

Gnomad EAS exome

AF:

0.777

Gnomad FIN exome

AF:

0.922

Gnomad NFE exome

AF:

0.889

Gnomad OTH exome

AF:

0.869

GnomAD4 exome

AF:

0.876

AC:

1276126

AN:

1456454

Hom.:

561059

Cov.:

AF XY:

0.871

AC XY:

631490

AN XY:

724848

show subpopulations

African (AFR)

AF:

0.973

AC:

32510

AN:

33406

American (AMR)

AF:

0.853

AC:

38122

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.863

AC:

22534

AN:

26098

East Asian (EAS)

AF:

0.777

AC:

30804

AN:

39662

South Asian (SAS)

AF:

0.717

AC:

61730

AN:

86108

European-Finnish (FIN)

AF:

0.920

AC:

48655

AN:

52894

Middle Eastern (MID)

AF:

0.831

AC:

4784

AN:

5756

European-Non Finnish (NFE)

AF:

0.889

AC:

984418

AN:

1107648

Other (OTH)

AF:

0.873

AC:

52569

AN:

60212

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

8318

16636

24953

33271

41589

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21240

42480

63720

84960

106200

<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:

0.904

AC:

137727

AN:

152318

Hom.:

62523

Cov.:

AF XY:

0.901

AC XY:

67078

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.973

AC:

40459

AN:

41586

American (AMR)

AF:

0.874

AC:

13374

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.873

AC:

3031

AN:

3472

East Asian (EAS)

AF:

0.780

AC:

4033

AN:

5168

South Asian (SAS)

AF:

0.708

AC:

3421

AN:

4830

European-Finnish (FIN)

AF:

0.930

AC:

9874

AN:

10614

Middle Eastern (MID)

AF:

0.837

AC:

246

AN:

294

European-Non Finnish (NFE)

AF:

0.890

AC:

60552

AN:

68028

Other (OTH)

AF:

0.895

AC:

1893

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

678

1356

2034

2712

3390

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

900

1800

2700

3600

4500

<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:

0.884

Hom.:

92473

Bravo

AF:

0.907

EpiCase

AF:

0.888

EpiControl

AF:

0.888

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.014

(source)

DANN

Benign

0.54

PhyloP100

-7.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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