rs2140773

Positions:

• chr2-232648465-C-A
• chr2-232648465-C-G

Variant summary

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

The NM_025202.4(EFHD1):​c.303-14337C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 151,776 control chromosomes in the GnomAD database, including 28,369 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 0.61 (28369 hom., cov: 31)
• Consequence: EFHD1 NM_025202.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

Genes affected

EFHD1 (HGNC:29556): (EF-hand domain family member D1) This gene encodes a member of the EF-hand super family of calcium binding proteins, which are involved in a variety of cellular processes including mitosis, synaptic transmission, and cytoskeletal rearrangement. The protein encoded by this gene is composed of an N-terminal disordered region, proline-rich elements, two EF-hands, and a C-terminal coiled-coil domain. This protein has been shown to associate with the mitochondrial inner membrane, and in HeLa cells, acts as a novel mitochondrial calcium ion sensor for mitochondrial flash activation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFHD1	NM_025202.4	c.303-14337C>A		intron_variant		ENST00000264059.8	NP_079478.1
EFHD1	NM_001243252.2	c.15-14337C>A		intron_variant			NP_001230181.1
EFHD1	NM_001308395.2	c.-35+9981C>A		intron_variant			NP_001295324.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFHD1	ENST00000264059.8	c.303-14337C>A		intron_variant		1	NM_025202.4	ENSP00000264059.3
EFHD1	ENST00000409613.5	c.15-14337C>A		intron_variant		1		ENSP00000386556.1
EFHD1	ENST00000409708.5	c.-35+9981C>A		intron_variant		2		ENSP00000386243.1
EFHD1	ENST00000442845.1	n.*72+9981C>A		intron_variant		3		ENSP00000395119.1

Frequencies

GnomAD3 genomes AF: 0.606 AC: 91863 AN: 151658 Hom.: 28330 Cov.: 31

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.773

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.625

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

GnomAD4 genome AF: 0.606 AC: 91950 AN: 151776 Hom.: 28369 Cov.: 31 AF XY: 0.599 AC XY: 44444 AN XY: 74176

Gnomad4 AFR AF: 0.685

Gnomad4 AMR AF: 0.555

Gnomad4 ASJ AF: 0.475

Gnomad4 EAS AF: 0.338

Gnomad4 SAS AF: 0.668

Gnomad4 FIN AF: 0.532

Gnomad4 NFE AF: 0.600

Gnomad4 OTH AF: 0.627

Alfa AF: 0.605 Hom.: 24293

Bravo AF: 0.606

Asia WGS AF: 0.557 AC: 1937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.066
DANN	Benign	0.37

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: rs2140773; hg19: chr2-233513175;