Genetic Variant RCC1L:c.*663C>T (chr7-75042369-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_030798.5(RCC1L):c.*663C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 985,496 control chromosomes in the GnomAD database, including 174,158 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 0.53 ( 23341 hom., cov: 33)

Exomes 𝑓: 0.60 ( 150817 hom. )

Consequence

RCC1L
NM_030798.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.998

Publications

2 publications found

Variant links:

Genes affected

RCC1L (HGNC:14948): (RCC1 like) This gene encodes a protein containing regulator of chromosome condensation 1-like repeats. The encoded protein may function as a guanine nucleotide exchange factor. This gene is located in a region of chromosome 7 that is deleted in Williams-Beuren syndrome, a multisystem developmental disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

RCC1L 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 (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
RCC1L	NM_030798.5 link	c.*663C>T	3_prime_UTR_variant	Exon 11 of 11	ENST00000610322.5	NP_110425.2	Q96I51-1
RCC1L	NM_001363447.2 link	c.*663C>T	3_prime_UTR_variant	Exon 11 of 11		NP_001350376.1
RCC1L	NM_148842.3 link	c.1317+10342C>T	intron_variant	Intron 10 of 10		NP_683682.1	Q96I51-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RCC1L	ENST00000610322.5 link	c.*663C>T		3_prime_UTR_variant	Exon 11 of 11	1	NM_030798.5	ENSP00000480364.1		Q96I51-1
RCC1L	ENST00000614461.4 link	c.1317+10342C>T		intron_variant	Intron 10 of 10	1		ENSP00000477659.1		Q96I51-3

Frequencies

GnomAD3 genomes

AF:

0.530

AC:

80600

AN:

152018

Hom.:

23343

Cov.:

show subpopulations

Gnomad AFR

AF:

0.292

Gnomad AMI

AF:

0.707

Gnomad AMR

AF:

0.633

Gnomad ASJ

AF:

0.590

Gnomad EAS

AF:

0.884

Gnomad SAS

AF:

0.627

Gnomad FIN

AF:

0.662

Gnomad MID

AF:

0.459

Gnomad NFE

AF:

0.592

Gnomad OTH

AF:

0.552

GnomAD4 exome

AF:

0.599

AC:

499559

AN:

833360

Hom.:

150817

Cov.:

AF XY:

0.598

AC XY:

230134

AN XY:

384862

show subpopulations

African (AFR)

AF:

0.261

AC:

4114

AN:

15790

American (AMR)

AF:

0.705

AC:

708

AN:

1004

Ashkenazi Jewish (ASJ)

AF:

0.588

AC:

3030

AN:

5152

East Asian (EAS)

AF:

0.876

AC:

3181

AN:

3630

South Asian (SAS)

AF:

0.617

AC:

10151

AN:

16464

European-Finnish (FIN)

AF:

0.642

AC:

190

AN:

296

Middle Eastern (MID)

AF:

0.490

AC:

795

AN:

1622

European-Non Finnish (NFE)

AF:

0.605

AC:

460910

AN:

762094

Other (OTH)

AF:

0.603

AC:

16480

AN:

27308

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

15046

30092

45137

60183

75229

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17082

34164

51246

68328

85410

<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:

0.530

AC:

80607

AN:

152136

Hom.:

23341

Cov.:

AF XY:

0.538

AC XY:

40016

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.291

AC:

12099

AN:

41514

American (AMR)

AF:

0.634

AC:

9679

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.590

AC:

2046

AN:

3470

East Asian (EAS)

AF:

0.884

AC:

4572

AN:

5170

South Asian (SAS)

AF:

0.627

AC:

3026

AN:

4830

European-Finnish (FIN)

AF:

0.662

AC:

6996

AN:

10572

Middle Eastern (MID)

AF:

0.456

AC:

134

AN:

294

European-Non Finnish (NFE)

AF:

0.592

AC:

40259

AN:

67994

Other (OTH)

AF:

0.546

AC:

1153

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1783

3565

5348

7130

8913

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

702

1404

2106

2808

3510

<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:

0.530

Hom.:

2137

Bravo

AF:

0.521

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

6.9

(source)

DANN

Benign

0.90

PhyloP100

1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over