rs4664114

Variant names:

• chr2-152521945-T-C
• rs4664114
• NM_052905.4:c.120T>C

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_052905.4(FMNL2):​c.120T>C​(p.Asn40Asn) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 1,608,258 control chromosomes in the GnomAD database, including 370,392 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.68 (34857 hom., cov: 31)
  • Exomes 𝑓: 0.68 (335535 hom.)
• Consequence: FMNL2 NM_052905.4 splice_region, synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.84
• Publications: 24 publications found

Genes affected

FMNL2 (HGNC:18267): (formin like 2) This gene encodes a formin-related protein. Formin-related proteins have been implicated in morphogenesis, cytokinesis, and cell polarity. Alternatively spliced transcript variants encoding different isoforms have been described but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 2-152521945-T-C is Benign according to our data. Variant chr2-152521945-T-C is described in ClinVar as Benign. ClinVar VariationId is 1526376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.84 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052905.4. 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
	FMNL2	NM_052905.4	MANE Select	c.120T>C	p.Asn40Asn	splice_region synonymous	Exon 2 of 26	NP_443137.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMNL2	ENST00000288670.14	TSL:1 MANE Select	c.120T>C	p.Asn40Asn	splice_region synonymous	Exon 2 of 26	ENSP00000288670.9
	FMNL2	ENST00000475377.3	TSL:5	c.120T>C	p.Asn40Asn	splice_region synonymous	Exon 2 of 28	ENSP00000418959.3
	FMNL2	ENST00000850952.1		c.120T>C	p.Asn40Asn	splice_region synonymous	Exon 2 of 27	ENSP00000521036.1

Frequencies

GnomAD3 genomes AF: 0.676 AC: 102587 AN: 151862 Hom.: 34836 Cov.: 31

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.708

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.661

GnomAD2 exomes AF: 0.694 AC: 171716 AN: 247598 AF XY: 0.687

Gnomad AFR exome AF: 0.645

Gnomad AMR exome AF: 0.831

Gnomad ASJ exome AF: 0.603

Gnomad EAS exome AF: 0.738

Gnomad FIN exome AF: 0.705

Gnomad NFE exome AF: 0.661

Gnomad OTH exome AF: 0.681

GnomAD4 exome AF: 0.677 AC: 986407 AN: 1456278 Hom.: 335535 Cov.: 33 AF XY: 0.676 AC XY: 490171 AN XY: 724644

African (AFR) AF: 0.644 AC: 21461 AN: 33304

American (AMR) AF: 0.822 AC: 36603 AN: 44538

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 15752 AN: 26074

East Asian (EAS) AF: 0.744 AC: 29481 AN: 39620

South Asian (SAS) AF: 0.682 AC: 58582 AN: 85868

European-Finnish (FIN) AF: 0.699 AC: 37324 AN: 53364

Middle Eastern (MID) AF: 0.614 AC: 3529 AN: 5746

European-Non Finnish (NFE) AF: 0.671 AC: 743370 AN: 1107584

Other (OTH) AF: 0.670 AC: 40305 AN: 60180

GnomAD4 genome AF: 0.675 AC: 102648 AN: 151980 Hom.: 34857 Cov.: 31 AF XY: 0.678 AC XY: 50317 AN XY: 74242

African (AFR) AF: 0.644 AC: 26664 AN: 41420

American (AMR) AF: 0.745 AC: 11370 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 2092 AN: 3472

East Asian (EAS) AF: 0.746 AC: 3861 AN: 5174

South Asian (SAS) AF: 0.684 AC: 3285 AN: 4806

European-Finnish (FIN) AF: 0.708 AC: 7475 AN: 10554

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.674 AC: 45813 AN: 67968

Other (OTH) AF: 0.655 AC: 1384 AN: 2112

Alfa AF: 0.668 Hom.: 100740

Bravo AF: 0.677

Asia WGS AF: 0.682 AC: 2376 AN: 3478

EpiCase AF: 0.658

EpiControl AF: 0.666

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	13
DANN	Benign	0.90
PhyloP100		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=95/5	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		1.0
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

Other links and lift over

dbSNP: rs4664114; hg19: chr2-153378459; COSMIC: COSV56491305;