chr4-71758418-C-T

Position:

• chr4-71758418-C-T

Variant summary

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

The NM_000583.4(GC):​c.702-247G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0547 in 152,216 control chromosomes in the GnomAD database, including 551 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 0.055 (551 hom., cov: 32)
• Consequence: GC NM_000583.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GC	NM_000583.4	c.702-247G>A		intron_variant		ENST00000273951.13	NP_000574.2
GC	NM_001204306.1	c.702-247G>A		intron_variant			NP_001191235.1
GC	NM_001204307.1	c.759-247G>A		intron_variant			NP_001191236.1
GC	XM_006714177.3	c.702-247G>A		intron_variant			XP_006714240.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GC	ENST00000273951.13	c.702-247G>A		intron_variant		1	NM_000583.4	ENSP00000273951	P1

Frequencies

GnomAD3 genomes AF: 0.0546 AC: 8306 AN: 152098 Hom.: 549 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0643

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.0265

Gnomad FIN AF: 0.00640

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00144

Gnomad OTH AF: 0.0411

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

GnomAD4 genome AF: 0.0547 AC: 8332 AN: 152216 Hom.: 551 Cov.: 32 AF XY: 0.0551 AC XY: 4102 AN XY: 74426

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.0645

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.0263

Gnomad4 FIN AF: 0.00640

Gnomad4 NFE AF: 0.00144

Gnomad4 OTH AF: 0.0416

Alfa AF: 0.0413 Hom.: 136

Bravo AF: 0.0669

Asia WGS AF: 0.138 AC: 479 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.35
DANN	Benign	0.21

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: rs10488854; hg19: chr4-72624135;