4-71758418-C-T

Variant names:

• chr4-71758418-C-T
• rs10488854
• NM_000583.4:c.702-247G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.9).
• 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 rank	MANE	Protein	UniProt
GC	NM_000583.4	c.702-247G>A		intron_variant	Intron 6 of 12	ENST00000273951.13	NP_000574.2
GC	NM_001204307.1	c.759-247G>A		intron_variant	Intron 7 of 13		NP_001191236.1
GC	NM_001204306.1	c.702-247G>A		intron_variant	Intron 7 of 13		NP_001191235.1
GC	NM_001440458.1	c.702-247G>A		intron_variant	Intron 6 of 11		NP_001427387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GC	ENST00000273951.13	c.702-247G>A		intron_variant	Intron 6 of 12	1	NM_000583.4	ENSP00000273951.8

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

African (AFR) AF: 0.143 AC: 5920 AN: 41498

American (AMR) AF: 0.0645 AC: 985 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.194 AC: 1006 AN: 5174

South Asian (SAS) AF: 0.0263 AC: 127 AN: 4828

European-Finnish (FIN) AF: 0.00640 AC: 68 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00144 AC: 98 AN: 68026

Other (OTH) AF: 0.0416 AC: 88 AN: 2114

Alfa AF: 0.0582 Hom.: 377

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
PhyloP100		-1.4
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: rs10488854; hg19: chr4-72624135;