Genetic Variant NM_014053.4:c.-104G>A (chr1-212858349-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS1

The NM_014053.4(FLVCR1):c.-104G>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 0.0000971 in 1,111,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

FLVCR1
NM_014053.4 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.327

Publications

1 publications found

Variant links:

Genes affected

FLVCR1 (HGNC:24682): (FLVCR choline and heme transporter 1) This gene encodes a member of the major facilitator superfamily of transporter proteins. The encoded protein is a heme transporter that may play a critical role in erythropoiesis by protecting developing erythroid cells from heme toxicity. This gene may play a role in posterior column ataxia with retinitis pigmentosa and the hematological disorder Diamond-Blackfan syndrome. [provided by RefSeq, Jan 2011]

FLVCR1 links:

FLVCR1-DT (HGNC:39077): (FLVCR1 divergent transcript)

FLVCR1-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0000788 (12/152304) while in subpopulation EAS AF = 0.00233 (12/5158). AF 95% confidence interval is 0.00134. There are 0 homozygotes in GnomAd4. There are 8 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014053.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FLVCR1	NM_014053.4	MANE Select	c.-104G>A	5_prime_UTR	Exon 1 of 10	NP_054772.1	Q9Y5Y0-1
FLVCR1-DT	NR_027285.1		n.-211C>T	upstream_gene	N/A
FLVCR1-DT	NR_027286.1		n.-211C>T	upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FLVCR1	ENST00000366971.9	TSL:1 MANE Select	c.-104G>A	5_prime_UTR	Exon 1 of 10	ENSP00000355938.4	Q9Y5Y0-1
FLVCR1	ENST00000867613.1		c.-104G>A	5_prime_UTR	Exon 1 of 11	ENSP00000537672.1
FLVCR1	ENST00000971333.1		c.-104G>A	5_prime_UTR	Exon 1 of 10	ENSP00000641392.1

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00232

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000100

AC:

AN:

959518

Hom.:

Cov.:

AF XY:

0.0000785

AC XY:

AN XY:

471312

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20246

American (AMR)

AF:

0.00

AC:

AN:

16516

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15978

East Asian (EAS)

AF:

0.00306

AC:

AN:

30384

South Asian (SAS)

AF:

0.00

AC:

AN:

51452

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29546

Middle Eastern (MID)

AF:

0.000340

AC:

AN:

2942

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

750028

Other (OTH)

AF:

0.0000471

AC:

AN:

42426

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152304

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41582

American (AMR)

AF:

0.00

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00233

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00

Hom.:

Bravo

AF:

0.0000567

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Posterior column ataxia-retinitis pigmentosa syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

-0.33

PromoterAI

-0.091

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over