Genetic Variant NM_001446.5:c.182C>T (chr6-122780399-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001446.5(FABP7):c.182C>T(p.Thr61Met) variant causes a missense change. The variant allele was found at a frequency of 0.0012 in 1,613,978 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0014 ( 9 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 30 hom. )

Consequence

FABP7
NM_001446.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.92

Publications

14 publications found

Variant links:

Genes affected

FABP7 (HGNC:3562): (fatty acid binding protein 7) The gene encodes a small, highly conserved cytoplasmic protein that bind long-chain fatty acids and other hydrophobic ligands. The encoded protein is important in the establishment of the radial glial fiber in the developing brain. Alternative splicing and promoter usage results in multiple transcript variants encoding different isoforms. Pseudogenes of this gene are found on multiple chromosomes. [provided by RefSeq, Jan 2016]

FABP7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010001451).

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00139 (212/152220) while in subpopulation EAS AF = 0.036 (186/5168). AF 95% confidence interval is 0.0318. There are 9 homozygotes in GnomAd4. There are 115 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FABP7	NM_001446.5 link	c.182C>T	p.Thr61Met	missense_variant	Exon 2 of 4	ENST00000368444.8	NP_001437.1	O15540-1
FABP7	NM_001319039.2 link	c.182C>T	p.Thr61Met	missense_variant	Exon 2 of 3		NP_001305968.1	O15540-2
FABP7	NM_001319042.2 link	c.170C>T	p.Thr57Met	missense_variant	Exon 2 of 4		NP_001305971.1	A0A077H155
FABP7	NM_001319041.2 link	c.182C>T	p.Thr61Met	missense_variant	Exon 2 of 2		NP_001305970.1	Q59HE4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FABP7	ENST00000368444.8 link	c.182C>T	p.Thr61Met	missense_variant	Exon 2 of 4	1	NM_001446.5	ENSP00000357429.3		O15540-1
FABP7	ENST00000356535.4 link	c.182C>T	p.Thr61Met	missense_variant	Exon 2 of 3	1		ENSP00000348931.4		O15540-2

Frequencies

GnomAD3 genomes

AF:

0.00138

AC:

210

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0359

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00328

AC:

823

AN:

251170

AF XY:

0.00310

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0421

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00118

AC:

1718

AN:

1461758

Hom.:

Cov.:

AF XY:

0.00122

AC XY:

888

AN XY:

727156

show subpopulations

African (AFR)

AF:

0.000239

AC:

AN:

33476

American (AMR)

AF:

0.0000895

AC:

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.0368

AC:

1462

AN:

39696

South Asian (SAS)

AF:

0.00111

AC:

AN:

86224

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000243

AC:

AN:

1111968

Other (OTH)

AF:

0.00197

AC:

119

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

168

252

336

420

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00139

AC:

212

AN:

152220

Hom.:

Cov.:

AF XY:

0.00155

AC XY:

115

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.000313

AC:

AN:

41542

American (AMR)

AF:

0.000131

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.0360

AC:

186

AN:

5168

South Asian (SAS)

AF:

0.000830

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68020

Other (OTH)

AF:

0.00284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00119

Hom.:

Bravo

AF:

0.00178

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00316

AC:

384

Asia WGS

AF:

0.0150

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

T;.

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.92

D;D

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.8

M;M

PhyloP100

4.9

PrimateAI

Uncertain

0.68

PROVEAN

Pathogenic

-4.8

D;D

REVEL

Benign

0.24

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.020

D;D

Polyphen

1.0

D;.

Vest4

0.82

MVP

0.62

MPC

0.52

ClinPred

0.075

GERP RS

3.6

Varity_R

0.88

gMVP

0.68

Mutation Taster

=89/11

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over