rs1051760

Variant names:

• chr7-150373541-A-G
• rs1051760
• NM_001099695.2:c.*596A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001099695.2(REPIN1):​c.*596A>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 0.396 in 169,878 control chromosomes in the GnomAD database, including 14,127 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 0.39 (12607 hom., cov: 33)
  • Exomes 𝑓: 0.41 (1520 hom.)
• Consequence: REPIN1 NM_001099695.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.300
• Publications: 19 publications found

Genes affected

REPIN1 (HGNC:17922): (replication initiator 1) Enables RNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within positive regulation of glucose import and regulation of fatty acid transport. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF775 (HGNC:28501): (zinc finger protein 775) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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 (AFR) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099695.2. 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
	REPIN1	NM_001099695.2	MANE Select	c.*596A>G		3_prime_UTR	Exon 3 of 3	NP_001093165.1
	REPIN1	NM_001388037.1		c.*596A>G		3_prime_UTR	Exon 3 of 3	NP_001374966.1
	REPIN1	NM_001362745.2		c.*596A>G		3_prime_UTR	Exon 3 of 3	NP_001349674.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REPIN1	ENST00000489432.7	TSL:2 MANE Select	c.*596A>G		3_prime_UTR	Exon 3 of 3	ENSP00000417291.2
	REPIN1	ENST00000444957.3	TSL:1	c.*596A>G		3_prime_UTR	Exon 2 of 2	ENSP00000407714.1
	REPIN1	ENST00000397281.6	TSL:2	c.*596A>G		3_prime_UTR	Exon 4 of 4	ENSP00000380451.2

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59906 AN: 151878 Hom.: 12583 Cov.: 33

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.342

GnomAD4 exome AF: 0.406 AC: 7264 AN: 17882 Hom.: 1520 Cov.: 0 AF XY: 0.408 AC XY: 3518 AN XY: 8624

African (AFR) AF: 0.563 AC: 9 AN: 16

American (AMR) AF: 0.233 AC: 178 AN: 764

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6

East Asian (EAS) AF: 0.500 AC: 8 AN: 16

South Asian (SAS) AF: 0.496 AC: 139 AN: 280

European-Finnish (FIN) AF: 0.428 AC: 6187 AN: 14472

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.313 AC: 662 AN: 2114

Other (OTH) AF: 0.377 AC: 80 AN: 212

GnomAD4 genome AF: 0.395 AC: 59972 AN: 151996 Hom.: 12607 Cov.: 33 AF XY: 0.403 AC XY: 29901 AN XY: 74266

African (AFR) AF: 0.528 AC: 21888 AN: 41454

American (AMR) AF: 0.259 AC: 3961 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 1488 AN: 3468

East Asian (EAS) AF: 0.497 AC: 2565 AN: 5158

South Asian (SAS) AF: 0.478 AC: 2308 AN: 4824

European-Finnish (FIN) AF: 0.434 AC: 4579 AN: 10548

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21972 AN: 67944

Other (OTH) AF: 0.341 AC: 721 AN: 2112

Alfa AF: 0.347 Hom.: 31073

Bravo AF: 0.385

Asia WGS AF: 0.475 AC: 1653 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.5
DANN	Benign	0.43
PhyloP100		0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1051760; hg19: chr7-150070630; COSMIC: COSV68292347; COSMIC: COSV68292347;