1-45658416-C-G

Variant names:

• chr1-45658416-C-G
• rs6656279
• NM_021639.5:c.60+612G>C

Variant summary

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

The NM_021639.5(GPBP1L1):​c.60+612G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 151,860 control chromosomes in the GnomAD database, including 22,086 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 0.54 (22086 hom., cov: 31)
• Consequence: GPBP1L1 NM_021639.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.222
• Publications: 2 publications found

Genes affected

GPBP1L1 (HGNC:28843): (GC-rich promoter binding protein 1 like 1) Predicted to enable DNA binding activity and RNA binding activity. Predicted to be involved in regulation of transcription, DNA-templated. 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPBP1L1	NM_021639.5	c.60+612G>C		intron_variant	Intron 4 of 12	ENST00000355105.8	NP_067652.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPBP1L1	ENST00000355105.8	c.60+612G>C		intron_variant	Intron 4 of 12	1	NM_021639.5	ENSP00000347224.3
GPBP1L1	ENST00000290795.7	c.60+612G>C		intron_variant	Intron 3 of 11	5		ENSP00000290795.3

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81500 AN: 151742 Hom.: 22026 Cov.: 31

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.541

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.538 AC: 81634 AN: 151860 Hom.: 22086 Cov.: 31 AF XY: 0.536 AC XY: 39765 AN XY: 74198

African (AFR) AF: 0.574 AC: 23754 AN: 41378

American (AMR) AF: 0.489 AC: 7463 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1724 AN: 3466

East Asian (EAS) AF: 0.379 AC: 1956 AN: 5164

South Asian (SAS) AF: 0.513 AC: 2463 AN: 4804

European-Finnish (FIN) AF: 0.563 AC: 5919 AN: 10510

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.538 AC: 36557 AN: 67966

Other (OTH) AF: 0.547 AC: 1154 AN: 2108

Alfa AF: 0.544 Hom.: 2810

Bravo AF: 0.534

Asia WGS AF: 0.472 AC: 1646 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.8
DANN	Benign	0.72
PhyloP100		-0.22
Mutation Taster		=100/0	polymorphism (auto)

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: rs6656279; hg19: chr1-46124088;