rs6999

Positions:

• chr20-56518845-A-G

Variant summary

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

The NM_016407.5(RTF2):​c.*580A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 151,908 control chromosomes in the GnomAD database, including 13,434 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 0.41 (13430 hom., cov: 31)
  • Exomes 𝑓: 0.53 (4 hom.)
• Consequence: RTF2 NM_016407.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160

Genes affected

RTF2 (HGNC:15890): (replication termination factor 2) Enables DNA binding activity. Involved in cellular response to hydroxyurea and regulation of DNA stability. Located in replication fork. [provided by Alliance of Genome Resources, Apr 2022]

GCNT7 (HGNC:16099): (glucosaminyl (N-acetyl) transferase family member 7) Predicted to enable acetylglucosaminyltransferase activity. Predicted to be involved in protein glycosylation. Predicted to be located in Golgi membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

FAM209A (HGNC:16100): (family with sequence similarity 209 member A) Located in extracellular exosome and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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 (NFE) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RTF2	NM_016407.5	c.*580A>G		3_prime_UTR_variant	9/9	ENST00000357348.10
GCNT7	NR_160308.1	n.144-4540T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RTF2	ENST00000357348.10	c.*580A>G		3_prime_UTR_variant	9/9	1	NM_016407.5	P1
GCNT7	ENST00000243913.8	c.-929-4540T>C		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62503 AN: 151752 Hom.: 13426 Cov.: 31

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.0567

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.384

GnomAD4 exome AF: 0.526 AC: 20 AN: 38 Hom.: 4 Cov.: 0 AF XY: 0.450 AC XY: 9 AN XY: 20

Gnomad4 AFR exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.567

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.412 AC: 62536 AN: 151870 Hom.: 13430 Cov.: 31 AF XY: 0.406 AC XY: 30113 AN XY: 74194

Gnomad4 AFR AF: 0.431

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.0566

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.444

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.383

Alfa AF: 0.427 Hom.: 10742

Bravo AF: 0.403

Asia WGS AF: 0.197 AC: 688 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.55

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

LitVar

Other links and lift over

dbSNP: rs6999; hg19: chr20-55093901;