1-245082118-C-T

Variant names:

• chr1-245082118-C-T
• rs142888002
• NM_032328.4:c.219C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_032328.4(DRC8):​c.219C>T​(p.Phe73Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00421 in 1,612,568 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0042 (8 hom., cov: 33)
  • Exomes 𝑓: 0.0042 (36 hom.)
• Consequence: DRC8 NM_032328.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0370
• Publications: 3 publications found

Genes affected

DRC8 (HGNC:28166): (EF-hand calcium binding domain 2) The gene encodes a protein that contains two EF-hand calcium-binding domains although its function has yet to be determined. Alternatively spliced transcripts have been observed. [provided by RefSeq, Mar 2014]

ENSG00000305254 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.135).
• BP6: Variant 1-245082118-C-T is Benign according to our data. Variant chr1-245082118-C-T is described in ClinVar as Benign. ClinVar VariationId is 770503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.037 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00417 (635/152252) while in subpopulation AMR AF = 0.0198 (303/15296). AF 95% confidence interval is 0.018. There are 8 homozygotes in GnomAd4. There are 314 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032328.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRC8	NM_032328.4	MANE Select	c.219C>T	p.Phe73Phe	synonymous	Exon 5 of 8	NP_115704.1	Q5VUJ9-2
	DRC8	NM_001290327.2		c.249C>T	p.Phe83Phe	synonymous	Exon 5 of 8	NP_001277256.1
	DRC8	NM_001143943.1		c.219C>T	p.Phe73Phe	synonymous	Exon 4 of 7	NP_001137415.1	Q5VUJ9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFCAB2	ENST00000366523.6	TSL:3 MANE Select	c.219C>T	p.Phe73Phe	synonymous	Exon 5 of 8	ENSP00000355480.1	Q5VUJ9-2
	EFCAB2	ENST00000948553.1		c.345C>T	p.Phe115Phe	synonymous	Exon 5 of 8	ENSP00000618612.1
	EFCAB2	ENST00000923178.1		c.219C>T	p.Phe73Phe	synonymous	Exon 4 of 7	ENSP00000593237.1

Frequencies

GnomAD3 genomes AF: 0.00418 AC: 636 AN: 152134 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.000845

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0198

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00391

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00649 AC: 1629 AN: 250960 AF XY: 0.00534

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.0331

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000272

Gnomad FIN exome AF: 0.00162

Gnomad NFE exome AF: 0.00337

Gnomad OTH exome AF: 0.00507

GnomAD4 exome AF: 0.00421 AC: 6151 AN: 1460316 Hom.: 36 Cov.: 30 AF XY: 0.00401 AC XY: 2914 AN XY: 726578

African (AFR) AF: 0.000657 AC: 22 AN: 33464

American (AMR) AF: 0.0315 AC: 1409 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26116

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39690

South Asian (SAS) AF: 0.00128 AC: 110 AN: 86188

European-Finnish (FIN) AF: 0.00180 AC: 96 AN: 53414

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5764

European-Non Finnish (NFE) AF: 0.00388 AC: 4311 AN: 1110636

Other (OTH) AF: 0.00320 AC: 193 AN: 60372

GnomAD4 genome AF: 0.00417 AC: 635 AN: 152252 Hom.: 8 Cov.: 33 AF XY: 0.00422 AC XY: 314 AN XY: 74434

African (AFR) AF: 0.000842 AC: 35 AN: 41554

American (AMR) AF: 0.0198 AC: 303 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4830

European-Finnish (FIN) AF: 0.00104 AC: 11 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00391 AC: 266 AN: 68012

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

Alfa AF: 0.00315 Hom.: 1

Bravo AF: 0.00624

EpiCase AF: 0.00387

EpiControl AF: 0.00308

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	6.7
DANN	Benign	0.67
PhyloP100		0.037
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs142888002; hg19: chr1-245245420; COSMIC: COSV63656959; COSMIC: COSV63656959;