rs4436830

Variant names:

• chr17-30056691-A-G
• rs4436830
• NM_198529.4:c.2365+535A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198529.4(EFCAB5):​c.2365+535A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,212 control chromosomes in the GnomAD database, including 2,827 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 0.17 (2827 hom., cov: 32)
• Consequence: EFCAB5 NM_198529.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.398
• Publications: 9 publications found

Genes affected

EFCAB5 (HGNC:24801): (EF-hand calcium binding domain 5) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198529.4. 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
	EFCAB5	NM_198529.4	MANE Select	c.2365+535A>G		intron	N/A	NP_940931.3	A4FU69-1
	EFCAB5	NM_001145053.2		c.2197+535A>G		intron	N/A	NP_001138525.2	A4FU69-5
	EFCAB5	NR_026738.2		n.2528+535A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFCAB5	ENST00000394835.8	TSL:1 MANE Select	c.2365+535A>G		intron	N/A	ENSP00000378312.3	A4FU69-1
	EFCAB5	ENST00000588978.1	TSL:1	c.1759+535A>G		intron	N/A	ENSP00000465109.1	K7EJC3
	EFCAB5	ENST00000440741.7	TSL:1	n.2365+535A>G		intron	N/A	ENSP00000393095.2	A4FU69-2

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25486 AN: 152094 Hom.: 2824 Cov.: 32

Gnomad AFR AF: 0.0478

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.0298

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.167 AC: 25489 AN: 152212 Hom.: 2827 Cov.: 32 AF XY: 0.162 AC XY: 12091 AN XY: 74412

African (AFR) AF: 0.0476 AC: 1980 AN: 41566

American (AMR) AF: 0.162 AC: 2469 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 684 AN: 3470

East Asian (EAS) AF: 0.0297 AC: 154 AN: 5186

South Asian (SAS) AF: 0.112 AC: 543 AN: 4832

European-Finnish (FIN) AF: 0.239 AC: 2531 AN: 10584

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16477 AN: 67976

Other (OTH) AF: 0.167 AC: 352 AN: 2112

Alfa AF: 0.220 Hom.: 6035

Bravo AF: 0.158

Asia WGS AF: 0.0670 AC: 232 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	10
DANN	Benign	0.69
PhyloP100		0.40
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4436830;

hg19: chr17-28383709;