rs7375

chr7-75042369-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.998

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]

ACMG classification

Verdict is Benign. Variant got -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	HGVSp	Effect	#exon/exons	MANE	UniProt
RCC1L	NM_030798.5	c.*663C>T		3_prime_UTR_variant	11/11	ENST00000610322.5
RCC1L	NM_001363447.2	c.*663C>T		3_prime_UTR_variant	11/11
RCC1L	NM_148842.3	c.1317+10342C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RCC1L	ENST00000610322.5	c.*663C>T		3_prime_UTR_variant	11/11	1	NM_030798.5	P1
RCC1L	ENST00000614461.4	c.1317+10342C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80600 AN: 152018 Hom.: 23343 Cov.: 33

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.: 33 AF XY: 0.598 AC XY: 230134 AN XY: 384862

Gnomad4 AFR exome AF: 0.261

Gnomad4 AMR exome AF: 0.705

Gnomad4 ASJ exome AF: 0.588

Gnomad4 EAS exome AF: 0.876

Gnomad4 SAS exome AF: 0.617

Gnomad4 FIN exome AF: 0.642

Gnomad4 NFE exome AF: 0.605

Gnomad4 OTH exome AF: 0.603

GnomAD4 genome AF: 0.530 AC: 80607 AN: 152136 Hom.: 23341 Cov.: 33 AF XY: 0.538 AC XY: 40016 AN XY: 74366

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.634

Gnomad4 ASJ AF: 0.590

Gnomad4 EAS AF: 0.884

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.662

Gnomad4 NFE AF: 0.592

Gnomad4 OTH AF: 0.546

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
Dann	Benign	0.90
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

LitVar

Other links and lift over

dbSNP: rs7375; hg19: chr7-74456477;