19-41908499-G-A

Variant names:

• chr19-41908499-G-A
• rs555712600
• NM_001365103.2:c.794C>T

Variant summary

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

The NM_001365103.2(ERFL):​c.794C>T​(p.Ser265Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00402 in 1,231,662 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/7 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (2 hom., cov: 31)
  • Exomes 𝑓: 0.0043 (12 hom.)
• Consequence: ERFL NM_001365103.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.73

Genes affected

ERFL (HGNC:53894): (ETS repressor factor like) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific. Predicted to be involved in cell differentiation and regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ARHGEF1 (HGNC:681): (Rho guanine nucleotide exchange factor 1) Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein coupled receptors. The encoded protein may form complex with G proteins and stimulate Rho-dependent signals. Multiple alternatively spliced transcript variants have been found for this gene, but the full-length nature of some variants has not been defined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01830563).
• BP6: Variant 19-41908499-G-A is Benign according to our data. Variant chr19-41908499-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3388920.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERFL	NM_001365103.2	c.794C>T	p.Ser265Leu	missense_variant	Exon 6 of 6	ENST00000597630.3	NP_001352032.1
ARHGEF1	NM_001396003.1	c.2592+1696G>A		intron_variant	Intron 27 of 28		NP_001382932.1
ARHGEF1	NM_001396002.1	c.2493+1696G>A		intron_variant	Intron 26 of 27		NP_001382931.1
ARHGEF1	NR_173092.1	n.4253+1696G>A		intron_variant	Intron 29 of 30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERFL	ENST00000597630.3	c.794C>T	p.Ser265Leu	missense_variant	Exon 6 of 6	5	NM_001365103.2	ENSP00000491574.1
ARHGEF1	ENST00000599589.5	c.1863+1696G>A		intron_variant	Intron 18 of 20	1		ENSP00000469735.1
ARHGEF1	ENST00000698932.1	c.2592+1696G>A		intron_variant	Intron 27 of 28			ENSP00000514042.1
ARHGEF1	ENST00000698934.1	n.*17+1696G>A		intron_variant	Intron 29 of 30			ENSP00000514044.1

Frequencies

GnomAD3 genomes AF: 0.00204 AC: 311 AN: 152126 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.000941

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00356

Gnomad OTH AF: 0.00191

GnomAD4 exome AF: 0.00430 AC: 4637 AN: 1079418 Hom.: 12 Cov.: 31 AF XY: 0.00435 AC XY: 2215 AN XY: 509554

Gnomad4 AFR exome AF: 0.000348

Gnomad4 AMR exome AF: 0.00119

Gnomad4 ASJ exome AF: 0.00167

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000513

Gnomad4 FIN exome AF: 0.000664

Gnomad4 NFE exome AF: 0.00483

Gnomad4 OTH exome AF: 0.00286

GnomAD4 genome AF: 0.00204 AC: 311 AN: 152244 Hom.: 2 Cov.: 31 AF XY: 0.00167 AC XY: 124 AN XY: 74438

Gnomad4 AFR AF: 0.000939

Gnomad4 AMR AF: 0.000326

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00356

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00244 Hom.: 0

Bravo AF: 0.00200

TwinsUK AF: 0.00216 AC: 8

ALSPAC AF: 0.00597 AC: 23

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ERFL: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Benign	0.73
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.65	T
MetaRNN	Benign	0.018	T
GERP RS		1.9

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs555712600; hg19: chr19-42412651;