19-41908585-C-G

Variant names:

• chr19-41908585-C-G
• rs541109321
• NM_001365103.2:c.708G>C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001365103.2(ERFL):​c.708G>C​(p.Thr236Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00342 in 1,231,698 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0022 (2 hom., cov: 31)
  • Exomes 𝑓: 0.0036 (7 hom.)
• Consequence: ERFL NM_001365103.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.991

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 19-41908585-C-G is Benign according to our data. Variant chr19-41908585-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3770835.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.991 with no splicing effect.
• 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.708G>C	p.Thr236Thr	synonymous_variant	Exon 6 of 6	ENST00000597630.3	NP_001352032.1
ARHGEF1	NM_001396003.1	c.2592+1782C>G		intron_variant	Intron 27 of 28		NP_001382932.1
ARHGEF1	NM_001396002.1	c.2493+1782C>G		intron_variant	Intron 26 of 27		NP_001382931.1
ARHGEF1	NR_173092.1	n.4253+1782C>G		intron_variant	Intron 29 of 30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERFL	ENST00000597630.3	c.708G>C	p.Thr236Thr	synonymous_variant	Exon 6 of 6	5	NM_001365103.2	ENSP00000491574.1
ARHGEF1	ENST00000599589.5	c.1863+1782C>G		intron_variant	Intron 18 of 20	1		ENSP00000469735.1
ARHGEF1	ENST00000698932.1	c.2592+1782C>G		intron_variant	Intron 27 of 28			ENSP00000514042.1
ARHGEF1	ENST00000698934.1	n.*17+1782C>G		intron_variant	Intron 29 of 30			ENSP00000514044.1

Frequencies

GnomAD3 genomes AF: 0.00226 AC: 343 AN: 151882 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.000581

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000721

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00445

Gnomad OTH AF: 0.000959

GnomAD4 exome AF: 0.00358 AC: 3866 AN: 1079698 Hom.: 7 Cov.: 32 AF XY: 0.00359 AC XY: 1832 AN XY: 509732

Gnomad4 AFR exome AF: 0.000479

Gnomad4 AMR exome AF: 0.00143

Gnomad4 ASJ exome AF: 0.0000695

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000359

Gnomad4 FIN exome AF: 0.000995

Gnomad4 NFE exome AF: 0.00404

Gnomad4 OTH exome AF: 0.00224

GnomAD4 genome AF: 0.00224 AC: 341 AN: 152000 Hom.: 2 Cov.: 31 AF XY: 0.00205 AC XY: 152 AN XY: 74284

Gnomad4 AFR AF: 0.000579

Gnomad4 AMR AF: 0.000720

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00442

Gnomad4 OTH AF: 0.000949

Alfa AF: 0.00319 Hom.: 1

Bravo AF: 0.00208

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ERFL: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.0070
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs541109321; hg19: chr19-42412737;