chr7-150371488-C-G

Variant names:

• chr7-150371488-C-G
• rs544002526
• NM_001099695.2:c.418C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001099695.2(REPIN1):​c.418C>G​(p.Leu140Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000268 in 1,606,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: REPIN1 NM_001099695.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.48
• Publications: 0 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]

REPIN1-AS1 (HGNC:41201): (REPIN1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05584553).
• BS2: High AC in GnomAdExome4 at 42 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REPIN1	NM_001099695.2	MANE Select	c.418C>G	p.Leu140Val	missense	Exon 3 of 3	NP_001093165.1	Q9BWE0-4
	REPIN1	NM_001388037.1		c.424C>G	p.Leu142Val	missense	Exon 3 of 3	NP_001374966.1
	REPIN1	NM_001362745.2		c.418C>G	p.Leu140Val	missense	Exon 3 of 3	NP_001349674.1	Q9BWE0-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REPIN1	ENST00000489432.7	TSL:2 MANE Select	c.418C>G	p.Leu140Val	missense	Exon 3 of 3	ENSP00000417291.2	Q9BWE0-4
	REPIN1	ENST00000444957.3	TSL:1	c.247C>G	p.Leu83Val	missense	Exon 2 of 2	ENSP00000407714.1	Q9BWE0-3
	REPIN1	ENST00000466559.1	TSL:1	c.*132C>G		3_prime_UTR	Exon 2 of 2	ENSP00000418507.1	C9J0L4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152186 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000500 AC: 12 AN: 240008 AF XY: 0.0000759

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000169

GnomAD4 exome AF: 0.0000289 AC: 42 AN: 1454690 Hom.: 0 Cov.: 40 AF XY: 0.0000345 AC XY: 25 AN XY: 724010

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26082

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.000464 AC: 40 AN: 86152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47036

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111622

Other (OTH) AF: 0.0000332 AC: 2 AN: 60252

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152304 Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1 AN XY: 74460

African (AFR) AF: 0.00 AC: 0 AN: 41568

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000508 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000992 AC: 12

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	19
DANN	Uncertain	0.99
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.5
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.16
Sift4G	Benign	0.43	T
Vest4		0.22
MutPred		0.086		Gain of relative solvent accessibility (P = 0.0166)
MVP		0.46
ClinPred		0.12	T
GERP RS		4.7
PromoterAI		-0.020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.068
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs544002526; hg19: chr7-150068577;