rs1491709

Variant names:

• chr4-71747849-G-A
• rs1491709
• NM_000583.4:c.1396-1644C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-71747849-G-A
• chr4-71747849-G-C
• chr4-71747849-G-T

Variant summary

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

The NM_000583.4(GC):​c.1396-1644C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0722 in 152,164 control chromosomes in the GnomAD database, including 424 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 0.072 (424 hom., cov: 32)
• Consequence: GC NM_000583.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.654
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GC	NM_000583.4	c.1396-1644C>T		intron_variant	Intron 11 of 12	ENST00000273951.13	NP_000574.2
GC	NM_001204307.1	c.1453-1644C>T		intron_variant	Intron 12 of 13		NP_001191236.1
GC	NM_001204306.1	c.1396-1644C>T		intron_variant	Intron 12 of 13		NP_001191235.1
GC	NM_001440458.1	c.1263-1644C>T		intron_variant	Intron 10 of 11		NP_001427387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GC	ENST00000273951.13	c.1396-1644C>T		intron_variant	Intron 11 of 12	1	NM_000583.4	ENSP00000273951.8

Frequencies

GnomAD3 genomes AF: 0.0722 AC: 10983 AN: 152046 Hom.: 423 Cov.: 32

Gnomad AFR AF: 0.0731

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0614

Gnomad ASJ AF: 0.0689

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0180

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0731

Gnomad OTH AF: 0.0723

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

GnomAD4 genome AF: 0.0722 AC: 10986 AN: 152164 Hom.: 424 Cov.: 32 AF XY: 0.0708 AC XY: 5269 AN XY: 74384

African (AFR) AF: 0.0732 AC: 3040 AN: 41530

American (AMR) AF: 0.0615 AC: 940 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0689 AC: 239 AN: 3468

East Asian (EAS) AF: 0.166 AC: 860 AN: 5170

South Asian (SAS) AF: 0.109 AC: 527 AN: 4822

European-Finnish (FIN) AF: 0.0180 AC: 191 AN: 10594

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0731 AC: 4967 AN: 67968

Other (OTH) AF: 0.0716 AC: 151 AN: 2110

Alfa AF: 0.0719 Hom.: 711

Bravo AF: 0.0752

Asia WGS AF: 0.0970 AC: 335 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.26
DANN	Benign	0.46
PhyloP100		-0.65
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: rs1491709; hg19: chr4-72613566;