chr7-150369842-C-T

Variant names:

• chr7-150369842-C-T
• rs374807951
• NM_001099695.2:c.131C>T

Variant summary

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

The NM_001099695.2(REPIN1):​c.131C>T​(p.Pro44Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 1,610,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: REPIN1 NM_001099695.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0380
• 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=0.024433464).
• BS2: High AC in GnomAd4 at 13 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.131C>T	p.Pro44Leu	missense	Exon 2 of 3	NP_001093165.1	Q9BWE0-4
	REPIN1	NM_001388037.1		c.140C>T	p.Pro47Leu	missense	Exon 2 of 3	NP_001374966.1
	REPIN1	NM_001362745.2		c.131C>T	p.Pro44Leu	missense	Exon 2 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.131C>T	p.Pro44Leu	missense	Exon 2 of 3	ENSP00000417291.2	Q9BWE0-4
	REPIN1	ENST00000444957.3	TSL:1	c.-15+901C>T		intron	N/A	ENSP00000407714.1	Q9BWE0-3
	REPIN1	ENST00000466559.1	TSL:1	c.39+901C>T		intron	N/A	ENSP00000418507.1	C9J0L4

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152200 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000101 AC: 25 AN: 248118 AF XY: 0.0000817

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000466

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000622

Gnomad OTH exome AF: 0.000333

GnomAD4 exome AF: 0.000121 AC: 176 AN: 1458728 Hom.: 0 Cov.: 30 AF XY: 0.000119 AC XY: 86 AN XY: 725172

African (AFR) AF: 0.0000299 AC: 1 AN: 33392

American (AMR) AF: 0.000359 AC: 16 AN: 44592

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26012

East Asian (EAS) AF: 0.00 AC: 0 AN: 39620

South Asian (SAS) AF: 0.00 AC: 0 AN: 86124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53334

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 0.000139 AC: 154 AN: 1109712

Other (OTH) AF: 0.0000830 AC: 5 AN: 60216

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152200 Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5 AN XY: 74332

African (AFR) AF: 0.0000241 AC: 1 AN: 41456

American (AMR) AF: 0.0000654 AC: 1 AN: 15292

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.0000805 Hom.: 0

Bravo AF: 0.0000907

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000121 AC: 1

ExAC AF: 0.000157 AC: 19

EpiCase AF: 0.000218

EpiControl AF: 0.000119

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	0.27
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0092	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.094	N
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.024	T
MetaSVM	Benign	-0.99	T
PhyloP100		-0.038
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-9.7	D
REVEL	Benign	0.053
Sift	Benign	0.069	T
Sift4G	Pathogenic	0.0	D
Vest4		0.17
MVP		0.093
MPC		0.67
ClinPred		0.22	T
GERP RS		3.1
gMVP		0.17
Mutation Taster		=292/8	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: rs374807951; hg19: chr7-150066931;