4-71769795-A-T

Variant names:

• chr4-71769795-A-T
• rs222017
• NM_000583.4:c.59-395T>A

Variant summary

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

The NM_000583.4(GC):​c.59-395T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.9 in 152,108 control chromosomes in the GnomAD database, including 61,743 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 0.90 (61743 hom., cov: 31)
• Consequence: GC NM_000583.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710

Genes affected

GC (HGNC:4187): (GC vitamin D binding protein) The protein encoded by this gene belongs to the albumin gene family. It is a multifunctional protein found in plasma, ascitic fluid, cerebrospinal fluid and on the surface of many cell types. It binds to vitamin D and its plasma metabolites and transports them to target tissues. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Feb 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GC	NM_000583.4	c.59-395T>A		intron_variant	Intron 1 of 12	ENST00000273951.13	NP_000574.2
GC	NM_001204307.1	c.116-395T>A		intron_variant	Intron 2 of 13		NP_001191236.1
GC	NM_001204306.1	c.59-395T>A		intron_variant	Intron 2 of 13		NP_001191235.1
GC	XM_006714177.3	c.59-395T>A		intron_variant	Intron 1 of 11		XP_006714240.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GC	ENST00000273951.13	c.59-395T>A		intron_variant	Intron 1 of 12	1	NM_000583.4	ENSP00000273951.8

Frequencies

GnomAD3 genomes AF: 0.900 AC: 136848 AN: 151990 Hom.: 61694 Cov.: 31

Gnomad AFR AF: 0.884

Gnomad AMI AF: 0.856

Gnomad AMR AF: 0.948

Gnomad ASJ AF: 0.969

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.962

Gnomad FIN AF: 0.815

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.897

Gnomad OTH AF: 0.917

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

GnomAD4 genome AF: 0.900 AC: 136955 AN: 152108 Hom.: 61743 Cov.: 31 AF XY: 0.899 AC XY: 66819 AN XY: 74332

Gnomad4 AFR AF: 0.884

Gnomad4 AMR AF: 0.948

Gnomad4 ASJ AF: 0.969

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.962

Gnomad4 FIN AF: 0.815

Gnomad4 NFE AF: 0.897

Gnomad4 OTH AF: 0.918

Alfa AF: 0.898 Hom.: 7620

Bravo AF: 0.907

Asia WGS AF: 0.979 AC: 3406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.2
DANN	Benign	0.60

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: rs222017; hg19: chr4-72635512;