dbSNP rs742014: FAM118A:c.523-960C>T (chr22-45329643-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017911.4(FAM118A):c.523-960C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 152,216 control chromosomes in the GnomAD database, including 18,775 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 0.44 ( 18771 hom., cov: 33)

Exomes 𝑓: 0.19 ( 4 hom. )

Consequence

FAM118A
NM_017911.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.77

Publications

6 publications found

Variant links:

Genes affected

FAM118A (HGNC:1313): (family with sequence similarity 118 member A) Enables identical protein binding activity. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

FAM118A links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_017911.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017911.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FAM118A	NM_017911.4	MANE Select	c.523-960C>T	intron	N/A	NP_060381.2	Q9NWS6-1
FAM118A	NM_001349916.2		c.565-960C>T	intron	N/A	NP_001336845.1
FAM118A	NM_001349914.2		c.526-960C>T	intron	N/A	NP_001336843.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FAM118A	ENST00000441876.7	TSL:1 MANE Select	c.523-960C>T	intron	N/A	ENSP00000395892.2	Q9NWS6-1
FAM118A	ENST00000894424.1		c.526-960C>T	intron	N/A	ENSP00000564483.1
FAM118A	ENST00000894426.1		c.526-960C>T	intron	N/A	ENSP00000564485.1

Frequencies

GnomAD3 genomes

AF:

0.440

AC:

66871

AN:

152002

Hom.:

18732

Cov.:

show subpopulations

Gnomad AFR

AF:

0.791

Gnomad AMI

AF:

0.232

Gnomad AMR

AF:

0.421

Gnomad ASJ

AF:

0.318

Gnomad EAS

AF:

0.478

Gnomad SAS

AF:

0.432

Gnomad FIN

AF:

0.261

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.266

Gnomad OTH

AF:

0.416

GnomAD4 exome

AF:

0.188

AC:

AN:

Hom.:

Cov.:

AF XY:

0.143

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.167

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.171

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.560

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:

0.440

AC:

66974

AN:

152120

Hom.:

18771

Cov.:

AF XY:

0.439

AC XY:

32637

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.791

AC:

32831

AN:

41502

American (AMR)

AF:

0.420

AC:

6426

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.318

AC:

1101

AN:

3466

East Asian (EAS)

AF:

0.479

AC:

2478

AN:

5178

South Asian (SAS)

AF:

0.432

AC:

2083

AN:

4826

European-Finnish (FIN)

AF:

0.261

AC:

2761

AN:

10584

Middle Eastern (MID)

AF:

0.439

AC:

129

AN:

294

European-Non Finnish (NFE)

AF:

0.266

AC:

18063

AN:

67964

Other (OTH)

AF:

0.422

AC:

891

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1537

3074

4612

6149

7686

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

564

1128

1692

2256

2820

<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:

0.353

Hom.:

1553

Bravo

AF:

0.465

Asia WGS

AF:

0.508

AC:

1765

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.29

(source)

DANN

Benign

0.71

PhyloP100

-1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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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