rs73347508

Variant names:

• chr14-104713007-C-T
• rs73347508
• NM_022489.4:c.2775+15C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-104713007-C-T
• chr14-104713007-C-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.2775+15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,611,780 control chromosomes in the GnomAD database, including 1,856 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.062 (978 hom., cov: 33)
  • Exomes 𝑓: 0.0067 (878 hom.)
• Consequence: INF2 NM_022489.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.47
• Publications: 3 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=-0.9).
• BP6: Variant 14-104713007-C-T is Benign according to our data. Variant chr14-104713007-C-T is described in ClinVar as Benign. ClinVar VariationId is 261612.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.211 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.2775+15C>T		intron	N/A	NP_071934.3	Q27J81-1
	INF2	NM_001426862.1		c.2775+15C>T		intron	N/A	NP_001413791.1
	INF2	NM_001426863.1		c.2775+15C>T		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.2775+15C>T		intron	N/A	ENSP00000376410.4	Q27J81-1
	INF2	ENST00000617571.5	TSL:1	n.2775+15C>T		intron	N/A	ENSP00000483829.2	A0A087X118
	INF2	ENST00000675207.1		c.2871+15C>T		intron	N/A	ENSP00000502644.1	A0A6Q8PHA2

Frequencies

GnomAD3 genomes AF: 0.0621 AC: 9457 AN: 152164 Hom.: 977 Cov.: 33

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0232

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00107

Gnomad OTH AF: 0.0454

GnomAD2 exomes AF: 0.0163 AC: 4021 AN: 246684 AF XY: 0.0127

Gnomad AFR exome AF: 0.221

Gnomad AMR exome AF: 0.0111

Gnomad ASJ exome AF: 0.00602

Gnomad EAS exome AF: 0.0000558

Gnomad FIN exome AF: 0.0000467

Gnomad NFE exome AF: 0.000981

Gnomad OTH exome AF: 0.00882

GnomAD4 exome AF: 0.00673 AC: 9822 AN: 1459498 Hom.: 878 Cov.: 36 AF XY: 0.00589 AC XY: 4280 AN XY: 726064

African (AFR) AF: 0.218 AC: 7289 AN: 33456

American (AMR) AF: 0.0128 AC: 574 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00547 AC: 143 AN: 26120

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39690

South Asian (SAS) AF: 0.00176 AC: 152 AN: 86224

European-Finnish (FIN) AF: 0.0000385 AC: 2 AN: 51950

Middle Eastern (MID) AF: 0.0154 AC: 83 AN: 5392

European-Non Finnish (NFE) AF: 0.000610 AC: 678 AN: 1111676

Other (OTH) AF: 0.0149 AC: 899 AN: 60274

GnomAD4 genome AF: 0.0622 AC: 9465 AN: 152282 Hom.: 978 Cov.: 33 AF XY: 0.0600 AC XY: 4472 AN XY: 74474

African (AFR) AF: 0.214 AC: 8907 AN: 41528

American (AMR) AF: 0.0232 AC: 355 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00519 AC: 18 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00290 AC: 14 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00107 AC: 73 AN: 68026

Other (OTH) AF: 0.0449 AC: 95 AN: 2116

Alfa AF: 0.0328 Hom.: 78

Bravo AF: 0.0703

Asia WGS AF: 0.0120 AC: 44 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 (1)
-	-	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	-0.90
CADD	Benign	2.6
DANN	Benign	0.40
PhyloP100		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs73347508; hg19: chr14-105179344;