chr3-129031714-G-A

Position:

• chr3-129031714-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2 BP4_Strong BS1

The NM_001377500.1(EFCC1):​c.1138+854G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 152,302 control chromosomes in the GnomAD database, including 1 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 0.0010 (1 hom., cov: 32)
• Consequence: EFCC1 NM_001377500.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.67

Genes affected

EFCC1 (HGNC:25692): (EF-hand and coiled-coil domain containing 1) Predicted to enable calcium ion binding activity. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00103 (157/152302) while in subpopulation SAS AF= 0.0232 (112/4832). AF 95% confidence interval is 0.0197. There are 1 homozygotes in gnomad4. There are 105 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFCC1	NM_001377500.1	c.1138+854G>A		intron_variant		ENST00000683648.1	NP_001364429.1
EFCC1	NM_024768.3	c.1138+854G>A		intron_variant			NP_079044.2
EFCC1	XM_011513161.3	c.451+854G>A		intron_variant			XP_011511463.1
EFCC1	XM_011513164.3	c.250+854G>A		intron_variant			XP_011511466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFCC1	ENST00000683648.1	c.1138+854G>A		intron_variant			NM_001377500.1	ENSP00000507795
EFCC1	ENST00000436022.2	c.1138+854G>A		intron_variant		5		ENSP00000414597	P1
EFCC1	ENST00000481536.2	n.412+854G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00102 AC: 155 AN: 152184 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000917

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0232

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.00103 AC: 157 AN: 152302 Hom.: 1 Cov.: 32 AF XY: 0.00141 AC XY: 105 AN XY: 74470

Gnomad4 AFR AF: 0.000963

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0232

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000315 Hom.: 1

Bravo AF: 0.000382

Asia WGS AF: 0.00895 AC: 31 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	0.021
DANN	Benign	0.66

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: rs900314; hg19: chr3-128750557;