Genetic Variant NM_001365103.2:c.501C>G (chr19-41909175-G-C) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_001365103.2(ERFL):c.501C>G(p.Thr167Thr) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000926 in 1,079,580 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T167T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 9.3e-7 ( 0 hom. )

Consequence

ERFL
NM_001365103.2 splice_region, synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.28

Publications

0 publications found

Variant links:

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]

ERFL links:

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]

ARHGEF1 Gene-Disease associations (from GenCC):

immunodeficiency 62
Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

ARHGEF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP7

Synonymous conserved (PhyloP=1.28 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365103.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ERFL	NM_001365103.2	MANE Select	c.501C>G	p.Thr167Thr	splice_region synonymous	Exon 5 of 6	NP_001352032.1	A0A1W2PQ73
ARHGEF1	NM_001396003.1		c.2592+2372G>C		intron	N/A	NP_001382932.1
ARHGEF1	NM_001396002.1		c.2493+2372G>C		intron	N/A	NP_001382931.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ERFL	ENST00000597630.3	TSL:5 MANE Select	c.501C>G	p.Thr167Thr	splice_region synonymous	Exon 5 of 6	ENSP00000491574.1	A0A1W2PQ73
ARHGEF1	ENST00000599589.5	TSL:1	c.1863+2372G>C		intron	N/A	ENSP00000469735.1	M0QYC1
ARHGEF1	ENST00000698932.1		c.2592+2372G>C		intron	N/A	ENSP00000514042.1	A0A8V8TP90

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.26e-7

AC:

AN:

1079580

Hom.:

Cov.:

AF XY:

0.00000196

AC XY:

AN XY:

509656

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22970

American (AMR)

AF:

0.00

AC:

AN:

8424

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14394

East Asian (EAS)

AF:

0.00

AC:

AN:

26524

South Asian (SAS)

AF:

0.00

AC:

AN:

19504

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21106

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2918

European-Non Finnish (NFE)

AF:

0.00000109

AC:

AN:

920072

Other (OTH)

AF:

0.00

AC:

AN:

43668

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

9.8

(source)

DANN

Benign

0.62

PhyloP100

1.3

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over