rs11850821

Variant names:

• chr14-104708748-A-G
• rs11850821
• NM_022489.4:c.1949+16A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_022489.4(INF2):​c.1949+16A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,611,970 control chromosomes in the GnomAD database, including 16,737 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (5755 hom., cov: 33)
  • Exomes 𝑓: 0.098 (10982 hom.)
• Consequence: INF2 NM_022489.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -2.77
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 14-104708748-A-G is Benign according to our data. Variant chr14-104708748-A-G is described in ClinVar as Benign. ClinVar VariationId is 261605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

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.1949+16A>G		intron	N/A	NP_071934.3	Q27J81-1
	INF2	NM_001426862.1		c.1949+16A>G		intron	N/A	NP_001413791.1
	INF2	NM_001426863.1		c.1949+16A>G		intron	N/A	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.1949+16A>G		intron	N/A	ENSP00000376410.4	Q27J81-1
	INF2	ENST00000617571.5	TSL:1	n.1949+16A>G		intron	N/A	ENSP00000483829.2	A0A087X118
	INF2	ENST00000675207.1		c.2045+16A>G		intron	N/A	ENSP00000502644.1	A0A6Q8PHA2

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30819 AN: 152048 Hom.: 5735 Cov.: 33

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.0857

Gnomad FIN AF: 0.0477

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0951

Gnomad OTH AF: 0.188

GnomAD2 exomes AF: 0.107 AC: 26632 AN: 248692 AF XY: 0.103

Gnomad AFR exome AF: 0.504

Gnomad AMR exome AF: 0.0720

Gnomad ASJ exome AF: 0.112

Gnomad EAS exome AF: 0.0140

Gnomad FIN exome AF: 0.0533

Gnomad NFE exome AF: 0.0937

Gnomad OTH exome AF: 0.115

GnomAD4 exome AF: 0.0984 AC: 143589 AN: 1459804 Hom.: 10982 Cov.: 33 AF XY: 0.0979 AC XY: 71086 AN XY: 726244

African (AFR) AF: 0.520 AC: 17380 AN: 33424

American (AMR) AF: 0.0795 AC: 3554 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 3002 AN: 26126

East Asian (EAS) AF: 0.0106 AC: 421 AN: 39698

South Asian (SAS) AF: 0.0850 AC: 7335 AN: 86250

European-Finnish (FIN) AF: 0.0528 AC: 2766 AN: 52388

Middle Eastern (MID) AF: 0.158 AC: 911 AN: 5762

European-Non Finnish (NFE) AF: 0.0909 AC: 100966 AN: 1111130

Other (OTH) AF: 0.120 AC: 7254 AN: 60310

GnomAD4 genome AF: 0.203 AC: 30885 AN: 152166 Hom.: 5755 Cov.: 33 AF XY: 0.196 AC XY: 14572 AN XY: 74390

African (AFR) AF: 0.500 AC: 20719 AN: 41474

American (AMR) AF: 0.118 AC: 1800 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 420 AN: 3472

East Asian (EAS) AF: 0.0102 AC: 53 AN: 5174

South Asian (SAS) AF: 0.0848 AC: 409 AN: 4824

European-Finnish (FIN) AF: 0.0477 AC: 506 AN: 10614

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.0950 AC: 6462 AN: 67986

Other (OTH) AF: 0.189 AC: 400 AN: 2112

Alfa AF: 0.144 Hom.: 1413

Bravo AF: 0.220

Asia WGS AF: 0.0910 AC: 317 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	1	Focal segmental glomerulosclerosis 5;C4302667:Charcot-Marie-Tooth disease dominant intermediate E (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.011
DANN	Benign	0.67
PhyloP100		-2.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs11850821; hg19: chr14-105175085; COSMIC: COSV53031028; COSMIC: COSV53031028;