rs3861679

Variant names:

• chr14-104689843-G-A
• rs3861679
• NM_022489.4:c.-10+104G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-104689843-G-A
• chr14-104689843-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_022489.4(INF2):​c.-10+104G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0407 in 694,874 control chromosomes in the GnomAD database, including 744 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.041 (266 hom., cov: 32)
  • Exomes 𝑓: 0.041 (478 hom.)
• Consequence: INF2 NM_022489.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0540
• Publications: 1 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

ENSG00000258858 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 14-104689843-G-A is Benign according to our data. Variant chr14-104689843-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1254136.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.107 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.-10+104G>A		intron	N/A	NP_071934.3	Q27J81-1
	INF2	NM_001426862.1		c.-10+104G>A		intron	N/A	NP_001413791.1
	INF2	NM_001426863.1		c.-10+8261G>A		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.-10+104G>A		intron	N/A	ENSP00000376410.4	Q27J81-1
	INF2	ENST00000398337.8	TSL:1	c.-10+104G>A		intron	N/A	ENSP00000381380.4	Q27J81-3
	INF2	ENST00000896057.1		c.-10+104G>A		intron	N/A	ENSP00000566116.1

Frequencies

GnomAD3 genomes AF: 0.0408 AC: 6199 AN: 151872 Hom.: 267 Cov.: 32

Gnomad AFR AF: 0.00961

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0833

Gnomad EAS AF: 0.0989

Gnomad SAS AF: 0.0935

Gnomad FIN AF: 0.0350

Gnomad MID AF: 0.0382

Gnomad NFE AF: 0.0351

Gnomad OTH AF: 0.0426

GnomAD4 exome AF: 0.0406 AC: 22048 AN: 542894 Hom.: 478 AF XY: 0.0405 AC XY: 10301 AN XY: 254340

African (AFR) AF: 0.00551 AC: 56 AN: 10160

American (AMR) AF: 0.154 AC: 96 AN: 624

Ashkenazi Jewish (ASJ) AF: 0.0859 AC: 287 AN: 3342

East Asian (EAS) AF: 0.105 AC: 251 AN: 2382

South Asian (SAS) AF: 0.0911 AC: 982 AN: 10782

European-Finnish (FIN) AF: 0.0272 AC: 5 AN: 184

Middle Eastern (MID) AF: 0.0458 AC: 50 AN: 1092

European-Non Finnish (NFE) AF: 0.0392 AC: 19440 AN: 496492

Other (OTH) AF: 0.0494 AC: 881 AN: 17836

GnomAD4 genome AF: 0.0408 AC: 6203 AN: 151980 Hom.: 266 Cov.: 32 AF XY: 0.0431 AC XY: 3198 AN XY: 74280

African (AFR) AF: 0.00959 AC: 398 AN: 41516

American (AMR) AF: 0.111 AC: 1698 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0833 AC: 289 AN: 3468

East Asian (EAS) AF: 0.0992 AC: 507 AN: 5112

South Asian (SAS) AF: 0.0934 AC: 451 AN: 4828

European-Finnish (FIN) AF: 0.0350 AC: 369 AN: 10548

Middle Eastern (MID) AF: 0.0411 AC: 12 AN: 292

European-Non Finnish (NFE) AF: 0.0351 AC: 2385 AN: 67916

Other (OTH) AF: 0.0441 AC: 93 AN: 2110

Alfa AF: 0.0344 Hom.: 17

Bravo AF: 0.0479

Asia WGS AF: 0.0900 AC: 310 AN: 3450

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.4
DANN	Benign	0.86
PhyloP100		0.054
PromoterAI		-0.051	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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: rs3861679; hg19: chr14-105156180;