chr1-244970326-C-CCCTCA

Position:

• chr1-244970326-C-CCCTCA

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The XM_054328428.1(LOC124900416):​c.211_212insTGAGG​(p.Ter71LeufsTer8) variant causes a frameshift, stop lost, splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000743 in 1,345,258 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: LOC124900416 XM_054328428.1 frameshift, stop_lost, splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53

Genes affected

EFCAB2 (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]

LOC124900416 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in XM_054328428.1 Downstream stopcodon found after 301 codons.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFCAB2	NM_032328.4	c.-90-3_-90-2insCCTCA		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000366523.6	NP_115704.1
LOC124900416	XM_054328428.1	c.211_212insTGAGG	p.Ter71LeufsTer8	frameshift_variant, stop_lost, splice_region_variant, intron_variant	1/4		XP_054184403.1
LOC101928068	NR_111907.1	n.59-348_59-347insTGAGG		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFCAB2	ENST00000366523.6	c.-90-3_-90-2insCCTCA		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		3	NM_032328.4	ENSP00000355480	P1
	ENST00000607453.1	n.762_763insTGAGG		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome AF: 7.43e-7 AC: 1 AN: 1345258 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 665630

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.54e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 20

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-245133628;