rs7375

Variant names:

• chr7-75042369-G-A
• rs7375
• NM_030798.5:c.*663C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030798.5. 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
	RCC1L	NM_030798.5	MANE Select	c.*663C>T		3_prime_UTR	Exon 11 of 11	NP_110425.2	Q96I51-1
	RCC1L	NM_001363447.2		c.*663C>T		3_prime_UTR	Exon 11 of 11	NP_001350376.1
	RCC1L	NM_148842.3		c.1317+10342C>T		intron	N/A	NP_683682.1	Q96I51-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCC1L	ENST00000610322.5	TSL:1 MANE Select	c.*663C>T		3_prime_UTR	Exon 11 of 11	ENSP00000480364.1	Q96I51-1
	RCC1L	ENST00000614461.4	TSL:1	c.1317+10342C>T		intron	N/A	ENSP00000477659.1	Q96I51-3
	RCC1L	ENST00000954050.1		c.*663C>T		3_prime_UTR	Exon 11 of 11	ENSP00000624109.1

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

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

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

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

Alfa AF: 0.530 Hom.: 2137

Bravo AF: 0.521

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.9
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

Other links and lift over

dbSNP: rs7375; hg19: chr7-74456477;