3-15436540-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_033083.7(EAF1):c.725G>A(p.Arg242Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00446 in 1,590,876 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0036 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0046 (24 hom.)
• Consequence: EAF1 NM_033083.7 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.73

Genes affected

EAF1 (HGNC:20907): (ELL associated factor 1) Enables transcription elongation regulator activity. Involved in regulation of transcription elongation from RNA polymerase II promoter. Located in intercellular bridge and nuclear body. Part of transcription elongation factor complex. [provided by Alliance of Genome Resources, Apr 2022]

METTL6 (HGNC:28343): (methyltransferase 6, tRNA N3-cytidine) Enables enzyme binding activity. Involved in tRNA methylation. [provided by Alliance of Genome Resources, Apr 2022]

EAF1-AS1 (HGNC:42328): (EAF1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0064282715).
• BP6: Variant 3-15436540-G-A is Benign according to our data. Variant chr3-15436540-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2653597.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EAF1	NM_033083.7	c.725G>A	p.Arg242Gln	missense_variant	5/6	ENST00000396842.7
EAF1	XM_011534165.2	c.422G>A	p.Arg141Gln	missense_variant	4/5
EAF1	XM_011534166.2	c.422G>A	p.Arg141Gln	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EAF1	ENST00000396842.7	c.725G>A	p.Arg242Gln	missense_variant	5/6	1	NM_033083.7	P1
METTL6	ENST00000598878.1	c.-125+2638C>T		intron_variant		5
EAF1-AS1	ENST00000597949.1	n.447C>T		non_coding_transcript_exon_variant	3/3	5
EAF1	ENST00000449565.1	c.*384G>A		3_prime_UTR_variant, NMD_transcript_variant	4/5	2

Frequencies

GnomAD3 genomes AF: 0.00356 AC: 542 AN: 152124 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000942

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00720

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.000942

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00622

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00360 AC: 895 AN: 248794 Hom.: 6 AF XY: 0.00398 AC XY: 537 AN XY: 134810

Gnomad AFR exome AF: 0.00101

Gnomad AMR exome AF: 0.00212

Gnomad ASJ exome AF: 0.00632

Gnomad EAS exome AF: 0.0000545

Gnomad SAS exome AF: 0.00206

Gnomad FIN exome AF: 0.00134

Gnomad NFE exome AF: 0.00559

Gnomad OTH exome AF: 0.00411

GnomAD4 exome AF: 0.00456 AC: 6554 AN: 1438634 Hom.: 24 Cov.: 30 AF XY: 0.00458 AC XY: 3253 AN XY: 710404

Gnomad4 AFR exome AF: 0.000544

Gnomad4 AMR exome AF: 0.00237

Gnomad4 ASJ exome AF: 0.00634

Gnomad4 EAS exome AF: 0.0000257

Gnomad4 SAS exome AF: 0.00231

Gnomad4 FIN exome AF: 0.00156

Gnomad4 NFE exome AF: 0.00512

Gnomad4 OTH exome AF: 0.00576

GnomAD4 genome AF: 0.00355 AC: 541 AN: 152242 Hom.: 2 Cov.: 32 AF XY: 0.00320 AC XY: 238 AN XY: 74448

Gnomad4 AFR AF: 0.000939

Gnomad4 AMR AF: 0.00183

Gnomad4 ASJ AF: 0.00720

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.000942

Gnomad4 NFE AF: 0.00622

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00522 Hom.: 5

Bravo AF: 0.00332

TwinsUK AF: 0.00593 AC: 22

ALSPAC AF: 0.00337 AC: 13

ESP6500AA AF: 0.000910 AC: 4

ESP6500EA AF: 0.00547 AC: 47

ExAC AF: 0.00359 AC: 436

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

EAF1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.090
Cadd	Benign	22
Dann	Uncertain	1.0
DEOGEN2	Benign	0.011	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.0064	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.2	M
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.085
Sift	Benign	0.18	T
Sift4G	Benign	0.59	T
Polyphen		0.90	P
Vest4		0.37
MVP		0.72
MPC		0.37
ClinPred		0.035	T
GERP RS		5.9
Varity_R		0.11
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs144767041; hg19: chr3-15478047;