rs150811244

Variant names:

• chr14-104714774-G-A
• rs150811244
• NM_022489.4:c.3612G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-104714774-G-A
• chr14-104714774-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_022489.4(INF2):​c.3612G>A​(p.Ser1204Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000211 in 1,600,200 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0012 (2 hom., cov: 34)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: INF2 NM_022489.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.66
• Publications: 0 publications found

Genes affected

INF2 (HGNC:23791): (inverted formin 2) This gene represents a member of the formin family of proteins. It is considered a diaphanous formin due to the presence of a diaphanous inhibitory domain located at the N-terminus of the encoded protein. Studies of a similar mouse protein indicate that the protein encoded by this locus may function in polymerization and depolymerization of actin filaments. Mutations at this locus have been associated with focal segmental glomerulosclerosis 5.[provided by RefSeq, Aug 2010]

INF2 Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease dominant intermediate E

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)
• focal segmental glomerulosclerosis 5

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 14-104714774-G-A is Benign according to our data. Variant chr14-104714774-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 472858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.66 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00121 (184/152212) while in subpopulation AFR AF = 0.00426 (177/41558). AF 95% confidence interval is 0.00375. There are 2 homozygotes in GnomAd4. There are 86 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.
• BS2: High AC in GnomAd4 at 184 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022489.4. 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
	INF2	NM_022489.4	MANE Select	c.3612G>A	p.Ser1204Ser	synonymous	Exon 21 of 23	NP_071934.3	Q27J81-1
	INF2	NM_001426862.1		c.3612G>A	p.Ser1204Ser	synonymous	Exon 21 of 23	NP_001413791.1
	INF2	NM_001426863.1		c.3612G>A	p.Ser1204Ser	synonymous	Exon 21 of 23	NP_001413792.1	Q27J81-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INF2	ENST00000392634.9	TSL:5 MANE Select	c.3612G>A	p.Ser1204Ser	synonymous	Exon 21 of 23	ENSP00000376410.4	Q27J81-1
	INF2	ENST00000617571.5	TSL:1	n.*461G>A		non_coding_transcript_exon	Exon 20 of 22	ENSP00000483829.2	A0A087X118
	INF2	ENST00000617571.5	TSL:1	n.*461G>A		3_prime_UTR	Exon 20 of 22	ENSP00000483829.2	A0A087X118

Frequencies

GnomAD3 genomes AF: 0.00118 AC: 179 AN: 152094 Hom.: 2 Cov.: 34

Gnomad AFR AF: 0.00413

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000279 AC: 62 AN: 221970 AF XY: 0.000228

Gnomad AFR exome AF: 0.00407

Gnomad AMR exome AF: 0.000159

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000305

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000106 AC: 154 AN: 1447988 Hom.: 0 Cov.: 37 AF XY: 0.000100 AC XY: 72 AN XY: 719720

African (AFR) AF: 0.00348 AC: 115 AN: 33010

American (AMR) AF: 0.000213 AC: 9 AN: 42210

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25286

East Asian (EAS) AF: 0.00 AC: 0 AN: 39462

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84614

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51440

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 0.00000813 AC: 9 AN: 1106546

Other (OTH) AF: 0.000335 AC: 20 AN: 59730

GnomAD4 genome AF: 0.00121 AC: 184 AN: 152212 Hom.: 2 Cov.: 34 AF XY: 0.00116 AC XY: 86 AN XY: 74420

African (AFR) AF: 0.00426 AC: 177 AN: 41558

American (AMR) AF: 0.000131 AC: 2 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67974

Other (OTH) AF: 0.00142 AC: 3 AN: 2110

Alfa AF: 0.000527 Hom.: 0

Bravo AF: 0.00139

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Focal segmental glomerulosclerosis 5;C4302667:Charcot-Marie-Tooth disease dominant intermediate E (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	INF2-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.28
DANN	Benign	0.75
PhyloP100		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs150811244; hg19: chr14-105181111;