rs141884370

Variant names:

• chr14-104689664-G-A
• rs141884370
• NM_022489.4:c.-85G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-104689664-G-A
• chr14-104689664-G-C

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.-85G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 982,220 control chromosomes in the GnomAD database, including 7,879 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.093 (885 hom., cov: 31)
  • Exomes 𝑓: 0.13 (6994 hom.)
• Consequence: INF2 NM_022489.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.148
• 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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 14-104689664-G-A is Benign according to our data. Variant chr14-104689664-G-A is described in ClinVar as Benign. ClinVar VariationId is 312673.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.132 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.-85G>A		5_prime_UTR	Exon 1 of 23	NP_071934.3	Q27J81-1
	INF2	NM_001426862.1		c.-85G>A		5_prime_UTR	Exon 1 of 23	NP_001413791.1
	INF2	NM_001031714.4		c.-85G>A		5_prime_UTR	Exon 1 of 22	NP_001026884.3	Q27J81-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INF2	ENST00000392634.9	TSL:5 MANE Select	c.-85G>A		5_prime_UTR	Exon 1 of 23	ENSP00000376410.4	Q27J81-1
	INF2	ENST00000398337.8	TSL:1	c.-85G>A		5_prime_UTR	Exon 1 of 5	ENSP00000381380.4	Q27J81-3
	INF2	ENST00000896057.1		c.-85G>A		5_prime_UTR	Exon 3 of 25	ENSP00000566116.1

Frequencies

GnomAD3 genomes AF: 0.0930 AC: 13994 AN: 150434 Hom.: 884 Cov.: 31

Gnomad AFR AF: 0.0227

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.0910

Gnomad ASJ AF: 0.0871

Gnomad EAS AF: 0.0546

Gnomad SAS AF: 0.0888

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.0952

GnomAD4 exome AF: 0.129 AC: 107130 AN: 831682 Hom.: 6994 Cov.: 27 AF XY: 0.129 AC XY: 49532 AN XY: 384086

African (AFR) AF: 0.0140 AC: 221 AN: 15768

American (AMR) AF: 0.0662 AC: 65 AN: 982

Ashkenazi Jewish (ASJ) AF: 0.0875 AC: 450 AN: 5142

East Asian (EAS) AF: 0.0394 AC: 143 AN: 3628

South Asian (SAS) AF: 0.0826 AC: 1357 AN: 16428

European-Finnish (FIN) AF: 0.0912 AC: 25 AN: 274

Middle Eastern (MID) AF: 0.0873 AC: 141 AN: 1616

European-Non Finnish (NFE) AF: 0.134 AC: 101684 AN: 760600

Other (OTH) AF: 0.112 AC: 3044 AN: 27244

GnomAD4 genome AF: 0.0930 AC: 13995 AN: 150538 Hom.: 885 Cov.: 31 AF XY: 0.0927 AC XY: 6820 AN XY: 73566

African (AFR) AF: 0.0227 AC: 937 AN: 41326

American (AMR) AF: 0.0908 AC: 1377 AN: 15160

Ashkenazi Jewish (ASJ) AF: 0.0871 AC: 301 AN: 3454

East Asian (EAS) AF: 0.0548 AC: 277 AN: 5056

South Asian (SAS) AF: 0.0895 AC: 426 AN: 4760

European-Finnish (FIN) AF: 0.124 AC: 1253 AN: 10092

Middle Eastern (MID) AF: 0.0753 AC: 22 AN: 292

European-Non Finnish (NFE) AF: 0.134 AC: 9034 AN: 67392

Other (OTH) AF: 0.0956 AC: 201 AN: 2102

Alfa AF: 0.106 Hom.: 136

Bravo AF: 0.0877

Asia WGS AF: 0.0580 AC: 199 AN: 3424

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Focal segmental glomerulosclerosis 5 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	14
DANN	Benign	0.94
PhyloP100		-0.15
PromoterAI		-0.11	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Mutation Taster		=300/0	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: rs141884370; hg19: chr14-105156001;